| 1. |
- Hellman, Jörgen, 1962
(author)
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The use of 'cultures' in official representations of Indonesia: The fiftieth anniversary of independence
- 1998
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In: Indonesia and the Malay World. - : Informa UK Limited. - 1363-9811 .- 1469-8382. ; 26:74, s. 1-12
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Journal article (peer-reviewed)abstract
- This article is an attempt to point out how official (that is, government sponsored and sanctioned) visions of 'Indonesia' are depicted in terms of 'culture' and 'art', and to further an analysis of the semantic and inner logic of the officially approved figure of Indonesia. Since president Suharto took power in Indonesia in 1965/66, words like kebudayaan (culture) and kesenian (art) have steadily gained importance in official representations of the Indonesian nation. The concepts are frequently utilized by the government to denote the idea that Indonesia consists of a certain number of 'cultures', which can each be presented by a unique set of art and aesthetics, stored in the design of, for example, the performing arts, houses, textiles, and clothes. As we shall see, the government presents this idea of 'Indonesia' in a way that leads one to understand the nation as a marriage of cultures.
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| 2. |
- Alalam, Hanna, et al.
(author)
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Global SLAM-Seq for accurate mRNA decay determination and identification of NMD targets.
- 2022
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In: RNA. - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 28:7
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Journal article (peer-reviewed)abstract
- Gene expression analysis requires accurate measurements of global RNA degradation rates, earlier problematic with methods disruptive to cell physiology. Recently, metabolic RNA labeling emerged as an efficient and minimally invasive technique applied in mammalian cells. Here, we have adapted SH-Linked Alkylation for the Metabolic Sequencing of RNA (SLAM-Seq) for a global mRNA stability study in yeast using 4-thiouracil pulse-chase labeling. We assign high-confidence half-life estimates for 67.5 % of expressed ORFs, and measure a median half-life of 9.4 min. For mRNAs where half-life estimates exist in the literature, their ranking order was in good agreement with previous data, indicating that SLAM-Seq efficiently classifies stable and unstable transcripts. We then leveraged our yeast protocol to identify targets of the Nonsense-mediated decay (NMD) pathway by measuring the change in RNA half-lives; instead of steady-state RNA level changes. With SLAM-Seq, we assign 580 transcripts as putative NMD targets, based on their measured half-lives in wild-type and upf3Δ mutants. We find 225 novel targets, and observe a strong agreement with previous reports of NMD targets, 61.2 % of our candidates being identified in previous studies. This indicates that SLAM-Seq is a simpler and more economic method for global quantification of mRNA half-lives. Our adaptation for yeast yielded global quantitative measures of the NMD effect on transcript half-lives, high correlation with RNA half-lives measured previously with more technically challenging protocols, and identification of novel NMD regulated transcripts that escaped prior detection.
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| 3. |
- Bateman, Alex, et al.
(author)
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RNAcentral: A vision for an international database of RNA sequences.
- 2011
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In: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 17:11, s. 1941-6
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Journal article (peer-reviewed)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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| 4. |
- Chavali, Sreenivas, et al.
(author)
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MicroRNAs act complementarily to regulate disease-related mRNA modules in human diseases
- 2013
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In: Rna-a Publication of the Rna Society. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 19:11, s. 1552-1562
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Journal article (peer-reviewed)abstract
- MicroRNAs (miRNAs) play a key role in regulating mRNA expression, and individual miRNAs have been proposed as diagnostic and therapeutic candidates. The identification of such candidates is complicated by the involvement of multiple miRNAs and mRNAs as well as unknown disease topology of the miRNAs. Here, we investigated if disease-associated miRNAs regulate modules of disease-associated mRNAs, if those miRNAs act complementarily or synergistically, and if single or combinations of miRNAs can be targeted to alter module functions. We first analyzed publicly available miRNA and mRNA expression data for five different diseases. Integrated target prediction and network-based analysis showed that the miRNAs regulated modules of disease-relevant genes. Most of the miRNAs acted complementarily to regulate multiple mRNAs. To functionally test these findings, we repeated the analysis using our own miRNA and mRNA expression data from CD4+ T cells from patients with seasonal allergic rhinitis. This is a good model of complex diseases because of its well-defined phenotype and pathogenesis. Combined computational and functional studies confirmed that miRNAs mainly acted complementarily and that a combination of two complementary miRNAs, miR-223 and miR-139-3p, could be targeted to alter disease-relevant module functions, namely, the release of type 2 helper T-cell (Th2) cytokines. Taken together, our findings indicate that miRNAs act complementarily to regulate modules of disease-related mRNAs and can be targeted to alter disease-relevant functions.
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| 5. |
- Davila Lopez, Marcela, et al.
(author)
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Early evolution of histone mRNA 3' end processing.
- 2008
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In: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 14:1, s. 1-10
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Journal article (peer-reviewed)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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| 6. |
- Farazi, Thalia A, et al.
(author)
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Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets.
- 2014
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In: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1469-9001 .- 1355-8382. ; 20, s. 1090-1102
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Journal article (peer-reviewed)abstract
- Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These RNA-binding proteins contain a single RNA recognition motif (RRM), and their targets and molecular function have not yet been identified. We defined transcriptome-wide RNA targets using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) in HEK293 cells, revealing exonic mature and intronic pre-mRNA binding sites, in agreement with the nuclear and cytoplasmic localization of the proteins. Computational and biochemical approaches defined the RNA recognition element (RRE) as a tandem CAC trinucleotide motif separated by a variable spacer region. Similar to other mRNA-binding proteins, RBPMS family of proteins relocalized to cytoplasmic stress granules under oxidative stress conditions suggestive of a support function for mRNA localization in large and/or multinucleated cells where it is preferentially expressed.
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| 7. |
- Holmqvist, Isak, et al.
(author)
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FLAME: long-read bioinformatics tool for comprehensive spliceome characterization
- 2021
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In: Rna. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 27:10, s. 1127-1139
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Journal article (peer-reviewed)abstract
- Comprehensive characterization of differentially spliced RNA transcripts with nanopore sequencing is limited by bioinformatics tools that are reliant on existing annotations. We have developed FLAME, a bioinformatics pipeline for alternative splicing analysis of gene-specific or transcriptome-wide long-read sequencing data. FLAME is a Python-based tool aimed at providing comprehensible quantification of full-length splice variants, reliable de novo recognition of splice sites and exons, and representation of consecutive exon connectivity in the form of a weighted adjacency matrix. Notably, this work-flow circumvents issues related to inadequate reference annotations and allows for incorporation of short-read sequencing data to improve the confidence of nanopore sequencing reads. In this study, the Epstein-Barr virus long noncoding RNA RPMS1 was used to demonstrate the utility of the pipeline. RPMS1 is ubiquitously expressed in Epstein-Barr virus associated cancer and known to undergo ample differential splicing. To fully resolve the RPMS1 spliceome, we combined gene-specific nanopore sequencing reads from a primary gastric adenocarcinoma and a nasopharyngeal carcinoma cell line with matched publicly available short-read sequencing data sets. All previously reported splice variants, including putative ORFs, were detected using FLAME. In addition, 32 novel exons, including two intron retentions and a cassette exon, were discovered within the RPMS1 gene.
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| 8. |
- Molin, Claes, 1977, et al.
(author)
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mRNA stability changes precede changes in steady-state mRNA amounts during hyperosmotic stress
- 2009
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In: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 15:4, s. 600-614
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Journal article (peer-reviewed)abstract
- Under stress, cells need to optimize the activity of a wide range of gene products during the response phases: shock, adaptation, and recovery. This requires coordination of several levels of regulation, including turnover and translation efficiencies ofmRNAs. Mitogen-activated protein (MAP) kinase pathways are implicated in many aspects of the environmental stress response,including initiation of transcription, translation efficiency, and mRNA turnover. In this study, we analyze mRNA turnover ratesand mRNA steady-state levels at different time points following mild hyperosmotic shock in Saccharomyces cerevisiae cells. Theregulation of mRNA stability is transient and affects most genes for which there is a change in transcript level. These changesprecede and prepare for the changes in steady-state levels, both regarding the initial increase and the later decline of stressinducedmRNAs. The inverse is true for stress-repressed genes, which become stabilized during hyperosmotic stress inpreparation of an increase as the cells recover. The MAP kinase Hog1 affects both steady-state levels and stability of stressresponsivetranscripts, whereas Rck2 influences steady-state levels without a major effect on stability. Regulation of mRNAstability is a wide-spread, but not universal, effect on stress-responsive transcripts during transient hyperosmotic stress. Bydestabilizing stress-induced mRNAs when their steady-state levels have reached a maximum, the cell prepares for thesubsequent recovery phase when these transcripts are to return to normal levels. Conversely, stabilization of stress-repressedmRNAs permits their rapid accumulation in the recovery phase. Our results show that mRNA turnover is coordinated withtranscriptional induction.
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| 9. |
- Nilsson, Daniel, 1978, et al.
(author)
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Cellular stress induces cytoplasmic RNA granules in fission yeast
- 2011
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In: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 17, s. 120-133
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Journal article (peer-reviewed)abstract
- Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2α does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.
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| 10. |
- Piccinelli, Paul, 1975, et al.
(author)
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Evolution of the iron-responsive element.
- 2007
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In: RNA (New York, N.Y.). - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 13:7, s. 952-66
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Journal article (peer-reviewed)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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