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- Appendino, G, et al.
(författare)
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SERCA-inhibiting activity of C-19 terpenolides from Thapsia garganica and their possible biogenesis
- 2005
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 68:8, s. 1213-1217
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Tidskriftsartikel (refereegranskat)abstract
- An investigation of Thapsia garganica afforded a series of tetracyclic C-19 dilactones, whose production was dependent on the time and location of the collection. These unusual tetrahomosesquiterpenoids are presumably biosynthesized via a carbon dioxide-triggered electrophilic polyolefin cyclization. Despite the structural differences with thapsigargin, these compounds showed SERCA-inhibiting properties.
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| 2. |
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| 4. |
- Hessle, Viktoria, et al.
(författare)
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The exosome Associates Cotranscriptionally with the Nascent Pre-mRNP through Interactions with Heterogeneous Nuclear Ribonucleoproteins
- 2009
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 20:15, s. 3459-3470
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Tidskriftsartikel (refereegranskat)abstract
- Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4 is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact with nascent pre-mRNPs. Our results lead to a revised mechanistic model for cotranscriptional quality control in which the exosome is constantly recruited to newly synthesized RNAs through direct interactions with specific hnRNP proteins.
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| 5. |
- Jin, Haining, et al.
(författare)
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Influences on gene expression in vivo by a Shine-Dalgarno sequence.
- 2006
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Ingår i: Mol Microbiol. - : Wiley. - 0950-382X .- 1365-2958. ; 60:2, s. 480-92
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Shine-Dalgarno (SD+: 5'-AAGGAGG-3') sequence anchors the mRNA by basepairing to the 16S rRNA in the small ribosomal subunit during translation initiation. We have here comparedhow an SD+ sequence influences gene expression, if located upstream or downstream of an initiation codon.The positive effect of an upstream SD+ is confirmed. A downstream SD+ gives decreased gene expression.This effect is also valid for appropriately modified natural Escherichia coli genes. If an SD+ is placedbetween two potential initiation codons, initiation takes place predominantly at the second start site.The first start site is activated if the distance between this site and the downstream SD+ is enlargedand/or if the second start site is weakened. Upstream initiation is eliminated if a stable stem-loopstructure is placed between this SD+ and the upstream start site. The results suggest that the two startsites compete for ribosomes that bind to an SD+ located between them. A minor positive contribution toupstream initiation resulting from 3' to 5' ribosomal diffusion along the mRNA is suggested. Analysisof the E. coli K12 genome suggests that the SD+ or SD-like sequences are systematically avoided in theearly coding region suggesting an evolutionary significance.
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| 6. |
- Macvanin, Mirjana, et al.
(författare)
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Transient erythromycin resistance phenotype associated with peptidyl-tRNA drop-off on early UGG and GGG codons
- 2007
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 189:24, s. 8993-9000
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Tidskriftsartikel (refereegranskat)abstract
- Expression of minigenes encoding tetra- or pentapeptides MXLX or MXLXV (E peptides), where X is a nonpolar amino acid, renders cells erythromycin resistant whereas expression of minigenes encoding tripeptide MXL does not. By using a 3A' reporter gene system beginning with an E-peptide-encoding sequence, we asked whether the codons UGG and GGG, which are known to promote peptidyl-tRNA drop-off at early positions in mRNA, would result in a phenotype of erythromycin resistance if located after this sequence. We find that UGG or GGG, at either position +4 or +5, without a following stop codon, is associated with an erythromycin resistance phenotype upon gene induction. Our results suggest that, while a stop codon at +4 gives a tripeptide product (MIL) and erythromycin sensitivity, UGG or GGG codons at the same position give a tetrapeptide product (MILW or MILG) and phenotype of erythromycin resistance. Thus, the drop-off event on GGG or UGG codons occurs after incorporation of the corresponding amino acid into the growing peptide chain. Drop-off gives rise to a peptidyl-tRNA where the peptide moiety functionally mimics a minigene peptide product of the type previously associated with erythromycin resistance. Several genes in Escherichia coli fulfill the requirements of high mRNA expression and an E-peptide sequence followed by UGG or GGG at position +4 or +5 and should potentially be able to give an erythromycin resistance phenotype.
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