| 1. |
- Lang, Tiange, 1976, et al.
(författare)
-
An inventory of mucin genes in the chicken genome shows that the mucin domain of Muc13 is encoded by multiple exons and that ovomucin is part of a locus of related gel-forming mucins.
- 2006
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Ingår i: BMC genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mucins are large glycoproteins that cover epithelial surfaces of the body. All mucins contain at least one PTS domain, a region rich in proline, threonine and serine. Mucins are also characterized by von Willebrand D (VWD) domains or SEA domains. We have developed computational methods to identify mucin genes and proteins based on these properties of the proteins. Using such methods we are able to characterize different organisms where genome sequence is available with respect to their mucin repertoire. RESULTS: We have here made a comprehensive analysis of potential mucins encoded by the chicken (Gallus gallus) genome. Three transmembrane mucins (Muc4, Muc13, and Muc16) and four gel-forming mucins (Muc6, Muc2, Muc5ac, and Muc5b) were identified. The gel-forming mucins are encoded within a locus similar to the corresponding human mucins. However, the chicken has an additional gene inserted between Muc2 and Muc5ac that encodes the the alpha-subunit of ovomucin, a protein similar to Muc2, but it is lacking a PTS domain. We also show that the beta-subunit of ovomucin is the orthologue of human MUC6. The transmembrane Muc13 gene is in chicken as well as in mammals adjacent to the HEG (heart of glass) gene. HEG has PTS, EGF and transmembrane domains like Muc13, suggesting that these two proteins are evolutionary related. Unlike previously known mucins, the PTS domain of Muc13 is encoded by multiple exons, where each exon encodes a repeat unit of the PTS domain. CONCLUSION: We report new mucin homologues in chicken and this information will aid in understanding the evolution of mucins in vertebrates. The fact that ovomucin, a protein not found in mammals, was located in the same locus as other gel-forming mucins provides strong support that these proteins are evolutionary related. Furthermore, a relationship of HEG and the transmembrane Muc13 is suggested on the basis of their biochemical properties and their presence in the same locus. Finally, our finding that the chicken Muc13 is distributed between multiple exons raises the interesting possibility that the length of the PTS domain could be controlled by alternative splicing.
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| 2. |
- Lang, Tiange, 1976, et al.
(författare)
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Bioinformatic identification of polymerizing and transmembrane mucins in the puffer fish Fugu rubripes
- 2004
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 14:6, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Mucins are large glycoproteins characterized by mucin domains that show little sequence conservation and are rich in the amino acids Ser, Thr, and Pro. To effectively predict mucins from genomic and protein sequences obtained from genome projects, we developed a strategy based on the amino acid compositional bias characteristic of the mucin domains. This strategy is combined with an analysis of other features commonly found in mucins. Our method has now been used to predict mucins in the puffer fish Fugu rubripes that were previously not identified or annotated. At least three gel-forming mucins were found with the same general domain structure as the human MUC2 mucin. In addition one transmembrane mucin was identified with SEA and EGF domains as found in the mammalian transmembrane mucins. These results suggest that the number of gel-forming mucins has been conserved during evolution of the vertebrates, whereas the family of transmembrane mucins has been markedly expanded in the higher vertebrates.
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| 3. |
- Lang, Tiange, 1976, et al.
(författare)
-
Gel-forming mucins appeared early in metazoan evolution.
- 2007
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 104:41, s. 16209-14
-
Tidskriftsartikel (refereegranskat)abstract
- Mucins are proteins that cover and protect epithelial cells and are characterized by domains rich in proline, threonine, and serine that are heavily glycosylated (PTS or mucin domains). Because of their sequence polymorphism, these domains cannot be used for evolutionary analysis. Instead, we have made use of the von Willebrand D (VWD) and SEA domains, typical for mucins. A number of animal genomes were examined for these domains to identify mucin homologues, and domains of the resulting proteins were used in phylogenetic studies. The frog Xenopus tropicalis stands out because the number of gel-forming mucins has markedly increased to at least 25 as compared with 5 for higher animals. Furthermore, the frog Muc2 homologues contain unique PTS domains where cysteines are abundant. This animal also has a unique family of secreted mucin-like proteins with alternating PTS and SEA domains, a type of protein also identified in the fishes. The evolution of the Muc4 mucin seems to have occurred by recruitment of a PTS domain to AMOP, NIDO, and VWD domains from a sushi domain-containing family of proteins present in lower animals, and Xenopus is the most deeply branching animal where a protein similar to the mammalian Muc4 was identified. All transmembrane mucins seem to have appeared in the vertebrate lineage, and the MUC1 mucin is restricted to mammals. In contrast, proteins with properties of the gel-forming mucins were identified also in the starlet sea anemone Nematostella vectensis, demonstrating an early origin of this group of mucins.
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| 4. |
- Lang, Tiange, 1976, et al.
(författare)
-
Searching the Evolutionary Origin of Epithelial Mucus Protein Components-Mucins and FCGBP
- 2016
-
Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:8, s. 1921-1936
-
Tidskriftsartikel (refereegranskat)abstract
- The gel-forming mucins are large glycosylated proteins that are essential components of the mucus layers covering epithelial cells. Using novel methods of identifying mucins based on profile hidden Markov models, we have found a large number of such proteins in Metazoa, aiding in their classification and allowing evolutionary studies. Most vertebrates have 5-6 gel-forming mucin genes and the genomic arrangement of these genes is well conserved throughout vertebrates. An exception is the frog Xenopus tropicalis with an expanded repertoire of at least 26 mucins of this type. Furthermore, we found that the ovomucin protein, originally identified in chicken, is characteristic of reptiles, birds, and amphibians. Muc6 is absent in teleost fish, but we now show that it is present in animals such as ghost sharks, demonstrating an early origin in vertebrate evolution. Public RNA-Seq data were analyzed with respect tomucins in zebrafish, frog, and chicken, thus allowing comparison in regard of tissue and developmental specificity. Analyses of invertebrate proteins reveal that gel-forming-mucin type of proteins is widely distributed also in this group. Their presence in Cnidaria, Porifera, and in Ctenophora (comb jellies) shows that these proteins were present early in metazoan evolution. Finally, we examined the evolution of the FCGBP protein, abundant in mucus and related to gel-forming mucins in terms of structure and localization. We demonstrate that FCGBP, ubiquitous in vertebrates, has a conserved N-terminal domain. Interestingly, this domain is also present as an N-terminal sequence in a number of bacterial proteins.
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| 5. |
- Simonsson, Stina, 1969, et al.
(författare)
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The herpes simplex virus type 1 origin binding protein: Specific recognition of phosphates and methyl groups defines the interacting surface for a monomeric DNA binding domain in the major groove of DNA
- 1998
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 273, s. 24633-24639
-
Tidskriftsartikel (refereegranskat)abstract
- The UL9 gene of herpes simplex virus type 1 (HSV-1) encodes an origin binding protein (OBP). It is an ATP-dependent DNA helicase and a sequence- specific DNA-binding protein. The latter function is carried out by the C- terminal domain of OBP (ΔOBP). We have now performed a quantitative analysis of the interaction between ΔOBP and its recognition sequence, GTTCGCAC, in oriS. Initially optimal conditions for binding were carefully determined. We observed that complexes with different electrophoretic mobilities were formed. A cross-linking experiment demonstrated that nonspecific complexes containing 2 or more protein monomers per DNA molecule were formed at high protein concentrations. The specific complex formed at low concentrations of ΔOBP had an electrophoretic mobility corresponding to a 1:1 complex. We then demonstrated that the methyl groups of thymine in the major groove were essential for high affinity binding. Changes in the minor groove had considerably smaller effects. Ethylation interference experiments indicated that specific contacts were made between OBP and three phosphates in the recognition sequence. Finally, these observations were used to present a model of the surface of DNA that interacts with ΔOBP in a sequence-specific manner.
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| 6. |
- Zhao, Zhiyuan, et al.
(författare)
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CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes
- 2017
-
Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 292:37, s. 15489-15500
-
Tidskriftsartikel (refereegranskat)abstract
- DNA replication greatly enhances expression of the herpes simplex virus 1 (HSV-1) gamma 2 late genes by still unknown mechanisms. Here, we demonstrate that 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK9, suppresses expression of gamma 2 late genes with an IC50 of 5 mu M, which is at least 10 times lower than the IC50 value required for inhibition of expression of early genes. The effect of DRB could not be explained by inhibition of DNA replication per se or loading of RNA polymerase II to late promoters and subsequent reduction of transcription. Instead, DRB reduces accumulation of gamma 2 late mRNA in the cytoplasm. In addition, we show that siRNA-mediated knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression. Finally, addition of DRB reduces co-immunoprecipitation of ICP27 using an anti-SPT5 antibody. Our results suggest that efficient expression of replication-dependent gamma 2 late genes is, at least in part, regulated by CDK9 dependent co-and/or post-transcriptional events involving SPT5 and ICP27.
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| 7. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
-
Identification and comparative analysis of components from the signal recognition particle in protozoa and fungi.
- 2004
-
Ingår i: BMC genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The signal recognition particle (SRP) is a ribonucleoprotein complex responsible for targeting proteins to the ER membrane. The SRP of metazoans is well characterized and composed of an RNA molecule and six polypeptides. The particle is organized into the S and Alu domains. The Alu domain has a translational arrest function and consists of the SRP9 and SRP14 proteins bound to the terminal regions of the SRP RNA. So far, our understanding of the SRP and its evolution in lower eukaryotes such as protozoa and yeasts has been limited. However, genome sequences of such organisms have recently become available, and we have now analyzed this information with respect to genes encoding SRP components. RESULTS: A number of SRP RNA and SRP protein genes were identified by an analysis of genomes of protozoa and fungi. The sequences and secondary structures of the Alu portion of the RNA were found to be highly variable. Furthermore, proteins SRP9/14 appeared to be absent in certain species. Comparative analysis of the SRP RNAs from different Saccharomyces species resulted in models which contain features shared between all SRP RNAs, but also a new secondary structure element in SRP RNA helix 5. Protein SRP21, previously thought to be present only in Saccharomyces, was shown to be a constituent of additional fungal genomes. Furthermore, SRP21 was found to be related to metazoan and plant SRP9, suggesting that the two proteins are functionally related. CONCLUSIONS: Analysis of a number of not previously annotated SRP components show that the SRP Alu domain is subject to a more rapid evolution than the other parts of the molecule. For instance, the RNA portion is highly variable and the protein SRP9 seems to have evolved into the SRP21 protein in fungi. In addition, we identified a secondary structure element in the Saccharomyces RNA that has been inserted close to the Alu region. Together, these results provide important clues as to the structure, function and evolution of SRP.
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| 8. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
-
Identification of chloroplast signal recognition particle RNA genes.
- 2004
-
Ingår i: Plant & cell physiology. - : Oxford University Press (OUP). - 0032-0781 .- 1471-9053. ; 45:11, s. 1633-9
-
Tidskriftsartikel (refereegranskat)abstract
- The signal recognition particle (SRP) is a ribonucleoprotein complex responsible for targeting proteins to the ER membrane in eukaryotes, the plasma membrane in bacteria and the thylakoid membrane in chloroplasts. In higher plants two different SRP-dependent mechanisms have been identified: one post-translational for proteins imported to the chloroplast and one co-translational for proteins encoded by the plastid genome. The post-translational chloroplast SRP (cpSRP) consists of the protein subunits cpSRP54 and cpSRP43. An RNA component has not been identified and does not seem to be required for the post-translational cpSRP. The co-translational mechanism is known to involve cpSRP54, but an RNA component has not yet been identified. Several chloroplast genomes have been sequenced recently, making a phylogenetically broad computational search for cpSRP RNA possible. We have analysed chloroplast genomes from 27 organisms. In higher plant chloroplasts, no SRP RNA genes were identified. However, eight plastids from red algae and Chlorophyta were found to contain an SRP RNA gene. These results suggest that SRP RNA forms a complex in these plastids with cpSRP54, reminiscent of the eubacterial SRP.
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| 9. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
-
Inventory and analysis of the protein subunits of the ribonucleases P and MRP provides further evidence of homology between the yeast and human enzymes.
- 2006
-
Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 34:18, s. 5145-56
-
Tidskriftsartikel (refereegranskat)abstract
- The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both enzymes in eukaryotes are composed of an RNA molecule and 9-12 protein subunits. Most of the protein subunits are shared between RNases P and MRP. We have here performed a computational analysis of the protein subunits in a broad range of eukaryotic organisms using profile-based searches and phylogenetic methods. A number of novel homologues were identified, giving rise to a more complete inventory of RNase P/MRP proteins. We present evidence of a relationship between fungal Pop8 and the protein subunit families Rpp14/Pop5 as well as between fungal Pop6 and metazoan Rpp25. These relationships further emphasize a structural and functional similarity between the yeast and human P/MRP complexes. We have also identified novel P and MRP RNAs and analysis of all available sequences revealed a K-turn motif in a large number of these RNAs. We suggest that this motif is a binding site for the Pop3/Rpp38 proteins and we discuss other structural features of the RNA subunit and possible relationships to the protein subunit repertoire.
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| 10. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
-
Kinship in the SRP RNA family
- 2009
-
Ingår i: RNA Biology. - 1547-6286. ; 6:5
-
Tidskriftsartikel (refereegranskat)abstract
- The signal recognition particle (SRP) is a ribonucleoprotein complex which participates in the targeting of protein to cellular membranes. The RNA component of the SRP has been found in all domains of life, but the size of the molecule and the number of RNA secondary structure elements vary considerably between the different phylogenetic groups. We continued our efforts to identify new SRP RNAs, compare their sequences, discover new secondary structure elements, conserved motifs, and other properties. We found additional proof for the variability in the apical loop of helix 8, and we identified several bacteria which lack all of their SRP components. Based on the distribution of SRP RNA features within the taxonomy, we suggest seven alignment groups: Bacteria with a small (4.5S) SRP RNA, Bacteria with a large (6S) SRP RNA, Archaea, Fungi (Ascomycota), Metazoa group, Protozoa group, and Plants. The proposed divisions improve the prediction of more distantly related SRP RNAs and provide a more inclusive representation of the SRP RNA family. Updates of the Rfam SRP RNA sequence collection are expected to benefit from the suggested groupings.
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| 11. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
-
SRPDB: Signal Recognition Particle Database
- 2003
-
Ingår i: Nucleic Acids Research. - 0305-1048. ; 31:1, s. 363-4
-
Tidskriftsartikel (refereegranskat)abstract
- The Signal Recognition Particle Database (SRPDB) at http://psyche.uthct.edu/dbs/SRPDB/SRPDB.html and http://bio.lundberg.gu.se/dbs/SRPDB/SRPDB.html assists in the better understanding of the structure and function of the signal recognition particle (SRP), a ribonucleoprotein complex that recognizes signal sequences as they emerge from the ribosome. SRPDB provides alphabetically and phylogenetically ordered lists of SRP RNA and SRP protein sequences. The SRP RNA alignment emphasizes base pairs supported by comparative sequence analysis to derive accurate SRP RNA secondary structures for each species. This release includes a total of 181 SRP RNA sequences, 7 protein SRP9, 11 SRP14, 31 SRP19, 113 SRP54 (Ffh), 9 SRP68 and 12 SRP72 sequences. There are 44 new sequences of the SRP receptor alpha subunit and its FtsY homolog (a total of 99 entries). Additional data are provided for polypeptides with established or potential roles in SRP-mediated protein targeting, such as the beta subunit of SRP receptor, Flhf, Hbsu and cpSRP43. Also available are motifs for the identification of new SRP RNA sequences, 2D representations, three-dimensional models in PDB format, and links to the high-resolution structures of several SRP components. New to this version of SRPDB is the introduction of a relational database system and a SRP RNA prediction server (SRP-Scan) which allows the identification of SRP RNAs within genome sequences and also generates secondary structure diagrams.
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| 12. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
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The enigmatic RNase MRP of kinetoplastids
- 2021
-
Ingår i: Rna Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 18:Supplement 1, s. 139-147
-
Tidskriftsartikel (refereegranskat)abstract
- The ribonucleoprotein RNase MRP is responsible for the processing of ribosomal RNA precursors. It is found in virtually all eukaryotes that have been examined. In the Euglenozoa, including the genera Euglena, Diplonema and kinetoplastids, MRP RNA and protein subunits have so far escaped detection using bioinformatic methods. However, we now demonstrate that the RNA component is widespread among the Euglenozoa and that these RNAs have secondary structures that conform to the structure of all other phylogenetic groups. In Euglena, we identified the same set of P/MRP protein subunits as in many other protists. However, we failed to identify any of these proteins in the kinetoplastids. This finding poses interesting questions regarding the structure and function of RNase MRP in these species.
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| 13. |
- Bartschat, Sebastian, et al.
(författare)
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U12 type introns were lost at multiple occasions during evolution.
- 2010
-
Ingår i: BMC genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Two categories of introns are known, a common U2 type and a rare U12 type. These two types of introns are removed by distinct spliceosomes. The phylogenetic distribution of spliceosomal RNAs that are characteristic of the U12 spliceosome, i.e. the U11, U12, U4atac and U6atac RNAs, suggest that U12 spliceosomes were lost in many phylogenetic groups. We have now examined the distribution of U2 and U12 introns in many of these groups. RESULTS: U2 and U12 introns were predicted by making use of available EST and genomic sequences. The results show that in species or branches where U12 spliceosomal components are missing, also U12 type of introns are lacking. Examples are the choanoflagellate Monosiga brevicollis, Entamoeba histolytica, green algae, diatoms, and the fungal lineage Basidiomycota. Furthermore, whereas U12 splicing does not occur in Caenorhabditis elegans, U12 introns as well as U12 snRNAs are present in Trichinella spiralis, which is deeply branching in the nematode tree. A comparison of homologous genes in T. spiralis and C. elegans revealed different mechanisms whereby U12 introns were lost. CONCLUSIONS: The phylogenetic distribution of U12 introns and spliceosomal RNAs give further support to an early origin of U12 dependent splicing. In addition, this distribution identifies a large number of instances during eukaryotic evolution where such splicing was lost.
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| 14. |
- Bateman, Alex, et al.
(författare)
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RNAcentral: A vision for an international database of RNA sequences.
- 2011
-
Ingår i: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 17:11, s. 1941-6
-
Tidskriftsartikel (refereegranskat)abstract
- During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor.
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| 15. |
- Carlsten, Jonas O P, et al.
(författare)
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Loss of the Mediator subunit Med20 affects transcription of tRNA and other non-coding RNA genes in fission yeast
- 2016
-
Ingår i: Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399. ; 1859:2, s. 339-347
-
Tidskriftsartikel (refereegranskat)abstract
- Mediator is a co-regulator of RNA polymerase II (Pol II), transducing signals from regulatory elements and transcription factors to the general transcription machinery at the promoter. We here demonstrate that Med20 influences ribosomal protein expression in fission yeast. In addition, loss of Med20 leads to an accumulation of aberrant, readthrough tRNA transcripts. These transcripts are polyadenylated and targeted for degradation by the exosome. Similarly, other non-coding RNA molecules, such as snRNA, snoRNA and rRNA, are also enriched in the polyadenylate preparations in the absence of Med20. We suggest that fission yeast Mediator takes part in a regulatory pathway that affects Pol III-dependent transcripts.
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| 16. |
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| 17. |
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| 18. |
- Davila Lopez, Marcela, et al.
(författare)
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Computational screen for spliceosomal RNA genes aids in defining the phylogenetic distribution of the major and minor spliceosomal components
- 2008
-
Ingår i: RNA Society Meeting 2008.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An essential step of gene expression is the removal of non-coding sequences (introns) from the pre-mRNA and the ligation of coding sequences (exons) to form the mature RNA (mRNA). It is known that the pre-mRNA splicing occurs by two sequential trans-esterification reactions and is catalyzed by a multicomponent complex, the spliceosome. Its assembly involves five small nuclear ribonucleoprotein particles (snRNPs) as well as an array of protein factors, which are determined by the class of intron to be spliced1. To date, two intron classes are known, U2- and U12-type introns. The U2-dependent spliceosome (panel a) is formed by the interaction of the U1, U2, U4/U6 and U5 snRNPs and numerous non-snRNP proteins with the pre-mRNA. The U12-dependent spliceosome (also referred to as the minor spliceosome, panel b), in contrast, consists of the U11, U12, U4atac/U6atac and U5 snRNPs with an unknown number of non-snRNP proteins. Thus, of the main spliceosomal subunits, only the U5 snRNA is common to both spliceosomes2.
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| 19. |
- Davila Lopez, Marcela, et al.
(författare)
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Conserved and variable domains of RNase MRP RNA
- 2009
-
Ingår i: RNA Biology. - 1547-6286. ; 6:3, s. 208-221
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Tidskriftsartikel (refereegranskat)abstract
- Ribonuclease MRP is a eukaryotic ribonucleoprotein complex consisting of one RNA molecule and 7-10 protein subunits. One important function of MRP is to catalyze an endonucleolytic cleavage during processing of rRNA precursors. RNase MRP is evolutionary related to RNase P which is critical for tRNA processing. A large number of MRP RNA sequences that now are available have been used to identify conserved primary and secondary structure features of the molecule. MRP RNA has structural features in common with P RNA such as a conserved catalytic core, but it also has unique features and is characterized by a domain highly variable between species. Information regarding primary and secondary structure features is of interest not only in basic studies of the function of MRP RNA, but also because mutations in the RNA give rise to human genetic diseases such as cartilage-hair hypoplasia.
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| 20. |
- Davila Lopez, Marcela, et al.
(författare)
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Early evolution of histone mRNA 3' end processing.
- 2008
-
Ingår i: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 14:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The replication-dependent histone mRNAs in metazoa are not polyadenylated, in contrast to the bulk of mRNA. Instead, they contain an RNA stem-loop (SL) structure close to the 3' end of the mature RNA, and this 3' end is generated by cleavage using a machinery involving the U7 snRNP and protein factors such as the stem-loop binding protein (SLBP). This machinery of 3' end processing is related to that of polyadenylation as protein components are shared between the systems. It is commonly believed that histone 3' end processing is restricted to metazoa and green algae. In contrast, polyadenylation is ubiquitous in Eukarya. However, using computational approaches, we have now identified components of histone 3' end processing in a number of protozoa. Thus, the histone mRNA stem-loop structure as well as the SLBP protein are present in many different protozoa, including Dictyostelium, alveolates, Trypanosoma, and Trichomonas. These results show that the histone 3' end processing machinery is more ancient than previously anticipated and can be traced to the root of the eukaryotic phylogenetic tree. We also identified histone mRNAs from both metazoa and protozoa that are polyadenylated but also contain the signals characteristic of histone 3' end processing. These results provide further evidence that some histone genes are regulated at the level of 3' end processing to produce either polyadenylated RNAs or RNAs with the 3' end characteristic of replication-dependent histone mRNAs.
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| 21. |
- Davila Lopez, Marcela, et al.
(författare)
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eGOB: eukaryotic Gene Order Browser.
- 2011
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Ingår i: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1460-2059 .- 1367-4803. ; 27:8, s. 1150-1
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genomes have been sequenced, allowing a range of comparative studies. Here, we present the eukaryotic Gene Order Browser with information on the order of protein and non-coding RNA (ncRNA) genes of 74 different eukaryotic species. The browser is able to display a gene of interest together with its genomic context in all species where that gene is present. Thereby, questions related to the evolution of gene organization and non-random gene order may be examined. The browser also provides access to data collected on pairs of adjacent genes that are evolutionarily conserved. AVAILABILITY: eGOB as well as underlying data are freely available at http://egob.biomedicine.gu.se SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: tore.samuelsson@medkem.gu.se.
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| 22. |
- Dumesic, Phillip A, et al.
(författare)
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Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans.
- 2015
-
Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 43:18, s. 9017-9027
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Tidskriftsartikel (refereegranskat)abstract
- Despite conservation of the signal recognition particle (SRP) from bacteria to man, computational approaches have failed to identify SRP components from genomes of many lower eukaryotes, raising the possibility that they have been lost or altered in those lineages. We report purification and analysis of SRP in the human pathogen Cryptococcus neoformans, providing the first description of SRP in basidiomycetous yeast. The C. neoformans SRP RNA displays a predicted structure in which the universally conserved helix 8 contains an unprecedented stem-loop insertion. Guided by this sequence, we computationally identified 152 SRP RNAs throughout the phylum Basidiomycota. This analysis revealed additional helix 8 alterations including single and double stem-loop insertions as well as loop diminutions affecting RNA structural elements that are otherwise conserved from bacteria to man. Strikingly, these SRP RNA features in Basidiomycota are accompanied by phylum-specific alterations in the RNA-binding domain of Srp54, the SRP protein subunit that directly interacts with helix 8. Our findings reveal unexpected fungal SRP diversity and suggest coevolution of the two most conserved SRP features-SRP RNA helix 8 and Srp54-in basidiomycetes. Because members of this phylum include important human and plant pathogens, these noncanonical features provide new targets for antifungal compound development.
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| 23. |
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| 24. |
- Gao, J., et al.
(författare)
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Evolution, diversification, and expression of KNOX proteins in plants
- 2015
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The KNOX (KNOTTED1-like homeobox) transcription factors play a pivotal role in leaf and meristem development. The majority of these proteins are characterized by the KNOX1, KNOX2, ELK, and homeobox domains whereas the proteins of the KNATM family contain only the KNOX domains. We carried out an extensive inventory of these proteins and here report on a total of 394 KNOX proteins from 48 species. The land plant proteins fall into two classes (I and II) as previously shown where the class I family seems to be most closely related to the green algae homologs. The KNATM proteins are restricted to Eudicots and some species have multiple paralogs of this protein. Certain plants are characterized by a significant increase in the number of KNOX paralogs; one example is Glycine max. Through the analysis of public gene expression data we show that the class II proteins of this plant have a relatively broad expression specificity as compared to class I proteins, consistent with previous studies of other plants. In G. max, class I protein are mainly distributed in axis tissues and KNATM paralogs are overall poorly expressed; highest expression is in the early plumular axis. Overall, analysis of gene expression in G. max demonstrates clearly that the expansion in gene number is associated with functional diversification.
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| 25. |
- Gariani, Talal, et al.
(författare)
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Conformational variability of the GTPase domain of the signal recognition particle receptor FtsY.
- 2006
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Ingår i: Journal of structural biology. - : Elsevier BV. - 1047-8477. ; 153:1, s. 85-96
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Tidskriftsartikel (refereegranskat)abstract
- The prokaryotic signal recognition particle Ffh and its receptor FtsY allow targeting of proteins into or across the plasma membrane. The targeting process is GTP dependent and the two proteins constitute a distinct GTPase family. The receptor FtsY is composed of A and NG domains where the NG's GTPase domain plays a critical role in the targeting process. In this study, we describe two X-ray structures determined independently of each other of the NG domain of FtsY from Mycoplasma mycoides (MmFtsY). The two structures are markedly different in three of the nucleotide-binding segments, GI (P-loop), GII, and GIII, making only one of the structures compatible with nucleotide binding. Interestingly, the two distinct conformations of the nucleotide-binding segments of MmFtsY are similar to the apo- and ADP-loaded forms of certain ATPases. The structure of the extended interface between the A and NG domains of MmFtsY provides new insights into the role of the A domain for phospholipid interaction.
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| 26. |
- He, L, et al.
(författare)
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Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis
- 2007
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Ingår i: Kidney International. - 1523-1755 .- 0085-2538. ; 71:9, s. 889-900
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Tidskriftsartikel (refereegranskat)abstract
- The kidney glomerulus plays a crucial role in blood filtration but the molecular composition and physiology of the glomerulus is not well understood. We previously constructed and large-scale sequenced four mouse glomerular expressed sequence tag (EST) libraries from newborn and adult mouse glomeruli. Here, we compared glomerular EST profiles with whole kidney EST profiles, thereby identifying 497 transcripts corresponding to UniGene clusters that were glomerulus-enriched, that is expressed more abundantly in glomeruli than in whole kidney. These include several known protein-coding glomerulus-specific transcripts critical for glomerulus development and function, but also a large number of gene transcripts, which have not previously been shown to be expressed in the glomerulus, or implicated in glomerular functions. We used in situ hybridization to demonstrate glomerulus-specific RNA expression for six novel glomerular genes and the public Human Protein Atlas to verify glomerular protein expression for another two. The higher mRNA abundance for the eight genes in glomeruli compared with whole kidney was also verified by Taqman quantitative polymerase chain reaction. We surmise that the further characterization of these genes and proteins will increase our understanding of glomerular development and physiology.
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| 27. |
- He, Liqun, et al.
(författare)
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The glomerular transcriptome and a predicted protein-protein interaction network
- 2008
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:2, s. 260-268
-
Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the molecular composition of the kidney glomerulus, we performed a meta-analysis of available glomerular transcriptional profiles made from mouse and man using five different methodologies. We generated a combined catalogue of glomerulus-enriched genes that emerged from these different sources and then used this to construct a predicted protein-protein interaction network in the glomerulus (GlomNet). The combined glomerulus-enriched gene catalogue provides the most comprehensive picture of the molecular composition of the glomerulus currently available, and GlomNet contributes an integrative systems biology approach to the understanding of glomerular signaling networks that operate during development, function, and disease.
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| 28. |
- Håkansson, Joakim, 1975, et al.
(författare)
-
Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion
- 2005
-
Ingår i: Tumour Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 26:2, s. 103-112
-
Tidskriftsartikel (refereegranskat)abstract
- To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.
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| 29. |
- Häsler, J, et al.
(författare)
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Useful 'junk': Alu RNAs in the human transcriptome.
- 2007
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Ingår i: Cellular and molecular life sciences : CMLS. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 64:14, s. 1793-800
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Tidskriftsartikel (refereegranskat)abstract
- Alu elements are the most abundant repetitive elements in the human genome; they have amplified by retrotransposition to reach the present number of more than one million copies. Alu elements can be transcribed in two different ways, by two independent polymerases. 'Free Alu RNAs' are transcribed by Pol III from their own promoter, while 'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs. Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression, for example by affecting protein translation, alternative splicing and mRNA stability. These discoveries illustrate how a part of the 'junk DNA' content of the human genome has been recruited to important functions in regulation of gene expression.
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| 30. |
- Isaksson, Åsa, 1974, et al.
(författare)
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Cell specific internal translation efficiency of Epstein-Barr virus present in solid organ transplant patients.
- 2007
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Ingår i: Journal of medical virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 79:5, s. 573-81
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Tidskriftsartikel (refereegranskat)abstract
- The U leader exon in the 5' untranslated region of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene contains an internal ribosome entry site, the EBNA internal ribosome entry segment (IRES), which promotes cap-independent translation and increases the expression level of the EBNA1 protein. It was previously reported that immunosuppressed organ transplanted patients showed an alternatively spliced EBNA1 transcript, excluding the EBNA IRES element. To further investigate the function of the EBNA IRES, sequence analysis of the EBNA IRES mRNA was performed in samples from seven organ transplant patients. Two nucleotide changes, G --> A at position 67531 and C --> U at position 67585 were found in the EBNA IRES mRNA, relative to the corresponding genomic Epstein-Barr virus (EBV) sequence in all patients. Moreover, the patient derived EBNA IRES mRNA was shown to differ from the IRES mRNA derived from the cell line B95.8 at position 67531 and from the cell lines Rael and P3HR1 at positions 67531 and 67585. cDNA from the various EBNA IRES sequences were cloned into bicistronic vectors, respectively, and used in transient transfection experiments in six human cell lines. The patient specific sequence significantly decreased the IRES activity in T-cells, while the base changes had no significant impact on the activity in B- or in epithelial cells. The genetic mechanisms behind EBV-associated diseases are complex, involving gene regulation by alternative promoters, alternative splicing, and translational control. The nucleotide changes in the patient specific EBNA IRES transcript and its influence on the translational activity, might illustrate new strategies utilised by the EBV to adapt to the immune control in patients with EBV associated diseases.
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| 31. |
- Jemt, Elisabeth, et al.
(författare)
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Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:19, s. 9262-9275
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Tidskriftsartikel (refereegranskat)abstract
- The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.
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| 32. |
- Jevtov, I., et al.
(författare)
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Zebrafish as a model to study live mucus physiology
- 2014
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Dysfunctional mucus barriers can result in important pulmonary and gastrointestinal conditions, but model systems to study the underlying causes are largely missing. We identified and characterized five mucin homologues in zebrafish, and demonstrated a strategy for fluorescence labeling of one selected mucin. These tools can be used for in vivo experiments and in pharmacological and genetic screens to study the dynamics and mechanisms of mucosal physiology.
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| 33. |
- Kalén, Mattias, et al.
(författare)
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Combination of reverse and chemical genetic screens reveals angiogenesis inhibitors and targets.
- 2009
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Ingår i: Chemistry & biology. - : Elsevier BV. - 1879-1301 .- 1074-5521. ; 16:4, s. 432-41
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Tidskriftsartikel (refereegranskat)abstract
- We combined reverse and chemical genetics to identify targets and compounds modulating blood vessel development. Through transcript profiling in mice, we identified 150 potentially druggable microvessel-enriched gene products. Orthologs of 50 of these were knocked down in a reverse genetic screen in zebrafish, demonstrating that 16 were necessary for developmental angiogenesis. In parallel, 1280 pharmacologically active compounds were screened in a human cell-based assay, identifying 28 compounds selectively inhibiting endothelial sprouting. Several links were revealed between the results of the reverse and chemical genetic screens, including the serine/threonine (S/T) phosphatases ppp1ca, ppp1cc, and ppp4c and an inhibitor of this gene family; Endothall. Our results suggest that the combination of reverse and chemical genetic screens, in vertebrates, is an efficient strategy for the identification of drug targets and compounds that modulate complex biological systems, such as angiogenesis.
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| 34. |
- Linder, Tomas, et al.
(författare)
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A family of putative transcription termination factors shared amongst metazoans and plants.
- 2005
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Ingår i: Current genetics. - : Springer Science and Business Media LLC. - 0172-8083 .- 1432-0983. ; 48:4, s. 265-9
-
Tidskriftsartikel (refereegranskat)abstract
- The human mitochondrial transcription termination factor (mTERF) is involved in the regulation of transcription of the mitochondrial genome. Similarity searches and phylogenetic analysis demonstrate that mTERF is a member of large and complex protein family (the MTERF family) shared amongst metazoans and plants. Interestingly, we identify three novel MTERF genes in vertebrates, which all encode proteins with predicted mitochondrial localization. Members of the MTERF family have so far not been detected in fungi, supporting the notion that mitochondrial transcription regulation may have evolved separately in yeast and animal cells.
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| 35. |
- Ludvigsson, Johnny, et al.
(författare)
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Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes
- 2021
-
Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560.
-
Tidskriftsartikel (refereegranskat)abstract
- Aim We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function. Material and Methods Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean +/- SD): 12.4 +/- 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 +/- 22.1 days. Baseline fasting C-peptide was 0.24 +/- 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 mu g, Diamyd (TM)) Day 30 and 60. They were followed for 30 months. Results No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-alpha increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration. Conclusions Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function.
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| 36. |
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| 37. |
- Malmberg, Erik, et al.
(författare)
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Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML
- 2019
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:2, s. 409-417
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p <.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p <.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
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| 38. |
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| 39. |
- Malmberg, Erik, et al.
(författare)
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Patient-tailored analysis of minimal residual disease in acute myeloid leukemia using next-generation sequencing
- 2017
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:1, s. 26-37
-
Tidskriftsartikel (refereegranskat)abstract
- Next-generation sequencing techniques have revealed that leukemic cells in acute myeloid leukemia often are characterized by a limited number of somatic mutations. These mutations can be the basis for the detection of leukemic cells in follow-up samples. The aim of this study was to identify leukemia-specific mutations in cells from patients with acute myeloid leukemia and to use these mutations as markers for minimal residual disease. Leukemic cells and normal lymphocytes were simultaneously isolated at diagnosis from 17 patients with acute myeloid leukemia using fluorescence-activated cell sorting. Exome sequencing of these cells identified 240 leukemia-specific single nucleotide variations and 22 small insertions and deletions. Based on estimated allele frequencies and their accuracies, 191 of these mutations qualified as candidates for minimal residual disease analysis. Targeted deep sequencing with a significance threshold of 0.027% for single nucleotide variations and 0.006% for NPM1 type A mutation was developed for quantification of minimal residual disease. When tested on follow-up samples from a patient with acute myeloid leukemia, targeted deep sequencing of single nucleotide variations as well as NPM1 was more sensitive than minimal residual disease quantification with multiparameter flow cytometry. In conclusion, we here describe how exome sequencing can be used for identification of leukemia-specific mutations in samples already at diagnosis of acute myeloid leukemia. We also show that targeted deep sequencing of such mutations, including single nucleotide variations, can be used for high-sensitivity quantification of minimal residual disease in a patient-tailored manner.
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| 40. |
- Padra, János T, et al.
(författare)
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Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and N-Acetylhexosamine-Containing O-Glycans, and Is Affected by Ca2
- 2017
-
Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 85:8
-
Tidskriftsartikel (refereegranskat)abstract
- Aeromonas salmonicida causes furunculosis in salmonids and is a threat to Atlantic salmon aquaculture. The epithelial surfaces that the pathogen colonizes are covered by a mucus layer predominantly comprised of secreted mucins. By using mass spectrometry to identify mucin glycan structures with and without enzymatic removal of glycan residues, coupled to measurements of bacterial growth, we show here that the complex Atlantic salmon intestinal mucin glycans enhance A. salmonicida growth, whereas the more simple skin mucin glycans do not. Of the glycan residues present terminally on the salmon mucins, only N-acetylglucosamine (GlcNAc) enhances growth. Sialic acids, which have an abundance of 75% among terminal glycans from skin and of <50% among intestinal glycans, cannot be removed or used by A. salmonicida for growth-enhancing purposes, and they shield internal GlcNAc from utilization. A Ca2+ concentration above 0.1 mM is needed for A. salmonicida to be able to utilize mucins for growth-promoting purposes, and 10 mM further enhances both A. salmonicida growth in response to mucins and binding of the bacterium to mucins. In conclusion, GlcNAc and sialic acids are important determinants of the A. salmonicida interaction with its host at the mucosal surface. Furthermore, since the mucin glycan repertoire affects pathogen growth, the glycan repertoire may be a factor to take into account during breeding and selection of strains for aquaculture.
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| 41. |
- Padra, Médea, 1986, et al.
(författare)
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Helicobacter suis binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes
- 2018
-
Ingår i: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 9:1, s. 898-918
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter suis colonizes the stomach of most pigs and is the most prevalent non-Helicobacter pylori Helicobacter species found in the human stomach. In the human host, H. suis contributes to the development of chronic gastritis, peptic ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis, decreased growth and ulcers. Here, we demonstrate that the level of H. pylori and H. suis binding to human and pig gastric mucins varies between individuals with species dependent specificity. The binding optimum of H. pylori is at neutral pH whereas that of H. suis has an acidic pH optimum, and the mucins that H. pylori bind to are different than those that H. suis bind to. Mass spectrometric analysis of mucin O-glycans from the porcine mucin showed that individual variation in binding is reflected by a difference in glycosylation; of 109 oligosaccharide structures identified, only 14 were present in all examined samples. H. suis binding to mucins correlated with glycans containing sulfate, sialic acid and terminal galactose. Among the glycolipids present in pig stomach, binding to lactotetraosylceramide (Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer) was identified, and adhesion to Gal beta 3GlcNAc beta 3Gal beta 4Glc at both acidic and neutral pH was confirmed using other glycoconjugates. Together with that H. suis bound to DNA (used as a proxy for acidic charge), we conclude that H. suis has two binding modes: one to glycans terminating with Gal beta 3GlcNAc, and one to negatively charged structures. Identification of the glycan structures H. suis interacts with can contribute to development of therapeutic strategies alternative to antibiotics.
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| 42. |
- Piccinelli, Paul, 1975, et al.
(författare)
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Evolution of the iron-responsive element.
- 2007
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Ingår i: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 13:7, s. 952-66
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Tidskriftsartikel (refereegranskat)abstract
- An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory proteins (IRPs) are key players in the control of iron metabolism in animal cells. They regulate translation initiation or mRNA stability, and the IRE is found in a variety of mRNAs, such as those encoding ferritin, transferrin receptor (Tfr), erythroid aminolevulinic acid synthase (eALAS), mitochondrial aconitase (mACO), ferroportin, and divalent metal transporter 1 (DMT1). We have studied the evolution of the IRE by considering all mRNAs previously known to be associated with this structure and by computationally examining its occurrence in a large variety of eukaryotic organisms. More than 100 novel sequences together with approximately 50 IREs that were previously reported resulted in a comprehensive view of the phylogenetic distribution of this element. A comparison of the different mRNAs shows that the IREs of eALAS and mACO are found in chordates, those of ferroportin and Tfr1 are found in vertebrates, and the IRE of DMT1 is confined to mammals. In contrast, the IRE of ferritin occurs in a majority of metazoa including lower metazoa such as sponges and Nematostella (sea anemone). These findings suggest that the ferritin IRE represents the ancestral version of this type of translational control and that during the evolution of higher animals the IRE structure was adopted by other genes. On the basis of primary sequence comparison between different organisms, we suggest that some of these IREs developed by "convergent evolution" through stepwise changes in sequence, rather than by recombination events.
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| 43. |
- Piccinelli, Paul, 1975, et al.
(författare)
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Identification and analysis of ribonuclease P and MRP RNA in a broad range of eukaryotes.
- 2005
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 33:14, s. 4485-95
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Tidskriftsartikel (refereegranskat)abstract
- RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA processing, respectively. The RNA subunits of these two enzymes are structurally related to each other and play an essential role in the enzymatic reaction. Both of the RNAs have a highly conserved helical region, P4, which is important in the catalytic reaction. We have used a bioinformatics approach based on conserved elements to computationally analyze available genomic sequences of eukaryotic organisms and have identified a large number of novel nuclear RNase P and MRP RNA genes. For MRP RNA for instance, this investigation increases the number of known sequences by a factor of three. We present secondary structure models of many of the predicted RNAs. Although all sequences are able to fold into the consensus secondary structure of P and MRP RNAs, a striking variation in size is observed, ranging from a Nosema locustae MRP RNA of 160 nt to much larger RNAs, e.g. a Plasmodium knowlesi P RNA of 696 nt. The P and MRP RNA genes appear in tandem in some protists, further emphasizing the close evolutionary relationship of these RNAs.
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| 44. |
- Regalia, Marco, et al.
(författare)
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Prediction of signal recognition particle RNA genes
- 2002
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Ingår i: Nucleic Acids Research. - 0305-1048. ; 30:15, s. 3368-77
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Tidskriftsartikel (refereegranskat)abstract
- We describe a method for prediction of genes that encode the RNA component of the signal recognition particle (SRP). A heuristic search for the strongly conserved helix 8 motif of SRP RNA is combined with covariance models that are based on previously known SRP RNA sequences. By screening available genomic sequences we have identified a large number of novel SRP RNA genes and we can account for at least one gene in every genome that has been completely sequenced. Novel bacterial RNAs include that of Thermotoga maritima, which, unlike all other non-gram-positive eubacteria, is predicted to have an Alu domain. We have also found the RNAs of Lactococcus lactis and Staphylococcus to have an unusual UGAC tetraloop in helix 8 instead of the normal GNRA sequence. An investigation of yeast RNAs reveals conserved sequence elements of the Alu domain that aid in the analysis of these RNAs. Analysis of the human genome reveals only two likely genes, both on chromosome 14. Our method for SRP RNA gene prediction is the first convenient tool for this task and should be useful in genome annotation.
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| 45. |
- Samuelsson, Bo, 1942, et al.
(författare)
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Structural characterization of blood group A glycolipids in blood group A liver tissue in situ perfused with O blood: the dominating presence of type 1 core chain A antigens.
- 2006
-
Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 13:2, s. 160-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biochemical studies of organ blood group antigen expression show a mixed pattern originating from both the organ tissue and remaining blood cells trapped in the organ despite in vitro perfusion of the vascular tree. The blood group A glycolipid expression was studied in a unique case in which a human liver had been in situ perfused by recipient blood. CASE HISTORY: A blood group O recipient was re-transplanted with an ABO incompatible A1Le (a - b +) liver. Because of discrepancy in size, liver segments II and III were removed 2 h after re-vascularization. Thereafter, the removed A1 liver segment was physiologically in situ perfused with O blood, eliminating a major part of the donor blood cells/plasma. EXPERIMENTAL: Total neutral glycolipids were isolated from the liver tissue and separated by high-performance liquid chromatography. Purified glycolipid fractions were stained with anti-A monoclonal antibodies (mAbs) and structurally characterized by mass spectrometry and proton nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Two blood group A reactive glycolipid compounds were isolated. One component had a thin-layer chromatography (TLC) mobility as a six-sugar glycolipid and reacted with mAbs specific for A type 1 mono-fucosyl structures. The second glycolipid fraction migrated as seven-sugar components and reacted with mAbs specific for type 1 difucosyl (ALeb) as well as Leb determinants. Mass spectrometry of the six-sugar component showed a structure similar to a blood group A hexaglycosylceramide with one fucose. Mass spectrometry and proton NMR spectroscopy of the seven-sugar fraction revealed a mixture of blood group Leb hexa- and ALeb hepta-glycosylceramides, respectively. All fractions were non-reactive with antibodies specific for A antigens based on types 3 and 4 core chain structures. In addition, TLC immunostaining of glycolipids isolated from blood group A livers, harvested for organ transplantation but discarded for various reasons, revealed trace amounts of several A glycolipids with a complex pattern. CONCLUSION: The in situ perfused liver tissue contains blood group A glycolipids based exclusively on type 1 core chains. The secretor gene (Se) codes for a fucosyltransferase acting on all core chain precursors while the H-gene fucosyltransferase only utilizes the type 2 chain precursor. Whether this explains that only A type 1 chain compounds were found has to be established.
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| 46. |
- Samuelsson, Tore, 1951, et al.
(författare)
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A histone 3' end processing machinery in protozoa
- 2007
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Ingår i: 5th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) & 6th European Conference on Computational Biology (ECCB).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In metazoa replication-dependent histone mRNAs are not polyadenylated. At the 3' end of these mRNAs there is a conserved sequence that contains a 16 nucleotide stem loop (SL) besides a purine rich sequences, called the histone downstream element (HDE) located several nucleotides downstream. This is necessary for endonucleolytic cleavage of pre-mRNA to release the mature mRNA. For this task also trans-acting factors are needed, such as a U7 snRNP, a stem loop binding protein (SLBP) and a subunit of the cleavage/polyadenylation specificity factor (CPSF-73)1,2. In order to understand the evolutionary origin of this molecular machinery we have computationally searched for all the transacting factors as well as the histone mRNA stem-loop structure in histone mRNAs in a range of eukaryotic species. We have used profile HMMs and covariance models to identify SL motifs as well as U7 RNA homologues in lower metazoa. Profile-based searches were used to identify proteins homologous to the mammalian SLBP. Surprisingly, a number of protozoan species seem to have the histone 3' end processing machinery characteristic of metazoa. These results show that this machinery is more ancient than previously anticipated.
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| 47. |
- Samuelsson, Tore, 1951
(författare)
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Genomics and bioinformatics - An introduction to programming tools for life scientists
- 2012
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- With the arrival of genomics and genome sequencing projects, biology has been transformed into an incredibly data-rich science. The vast amount of information generated has made computational analysis critical and has increased demand for skilled bioinformaticians. Designed for biologists without previous computer science experience, this textbook provides a hands-on introduction to Unix, Perl and other software used in sequence bioinformatics. Relevant biological topics are used throughout the book and are combined with practical bioinformatics examples, leading students through the process from biological problem to computational solution. All of the Perl scripts, sequence and database files used in the book are available for download at the accompanying website, allowing the reader to easily follow each example using their own computer. Programming examples are kept at an intorductory level, avoiding complex mathematics that students often find daunting and demonstrating that even simple programs can provide powerful solutions to many complex bioinformatics problems.
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| 48. |
- Sloth Andersen, Ebbe, et al.
(författare)
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The tmRDB and SRPDB resources.
- 2006
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 34:Database issue
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Tidskriftsartikel (refereegranskat)abstract
- Maintained at the University of Texas Health Science Center at Tyler, Texas, the tmRNA database (tmRDB) is accessible at the URL http://psyche.uthct.edu/dbs/tmRDB/tmRDB.html with mirror sites located at Auburn University, Auburn, Alabama (http://www.ag.auburn.edu/mirror/tmRDB/) and the Royal Veterinary and Agricultural University, Denmark (http://tmrdb.kvl.dk/). The signal recognition particle database (SRPDB) at http://psyche.uthct.edu/dbs/SRPDB/SRPDB.html is mirrored at http://srpdb.kvl.dk/ and the University of Goteborg (http://bio.lundberg.gu.se/dbs/SRPDB/SRPDB.html). The databases assist in investigations of the tmRNP (a ribonucleoprotein complex which liberates stalled bacterial ribosomes) and the SRP (a particle which recognizes signal sequences and directs secretory proteins to cell membranes). The curated tmRNA and SRP RNA alignments consider base pairs supported by comparative sequence analysis. Also shown are alignments of the tmRNA-associated proteins SmpB, ribosomal protein S1, alanyl-tRNA synthetase and Elongation Factor Tu, as well as the SRP proteins SRP9, SRP14, SRP19, SRP21, SRP54 (Ffh), SRP68, SRP72, cpSRP43, Flhf, SRP receptor (alpha) and SRP receptor (beta). All alignments can be easily examined using a new exploratory browser. The databases provide links to high-resolution structures and serve as depositories for structures obtained by molecular modeling.
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| 49. |
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| 50. |
- Spåhr, H, et al.
(författare)
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Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells.
- 2001
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 98:21, s. 11985-90
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Tidskriftsartikel (refereegranskat)abstract
- With the identification of eight new polypeptides, we here complete the subunit characterization of the Schizosaccharomyces pombe RNA polymerase II holoenzyme. The complex contains homologs to all 10 essential gene products present in the Saccharomyces cerevisiae Mediator, but lacks clear homologs to any of the 10 S. cerevisiae components encoded by nonessential genes. S. pombe Mediator instead contains three unique components (Pmc2, -3, and -6), which lack homologs in other cell types. Presently, pmc2(+) and pmc3(+) have been shown to be nonessential genes. The data suggest that S. pombe and S. cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10 essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated.
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