Distinct Roles of Non-Canonical Poly(A) Polymerases in RNA Metabolism
| Autor: | Stepanka Vanacova, Walter Keller, Salvatore San Paolo, Tanja Scherrer, André P. Gerber, Luca Schenk, Diana Blank |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Ribosomal Proteins
Cancer Research RNA Untranslated Saccharomyces cerevisiae Proteins Polyadenylation lcsh:QH426-470 RNA Stability DNA-Directed DNA Polymerase Saccharomyces cerevisiae Biology Exosomes 03 medical and health sciences Gene Expression Regulation Fungal Gene expression Genetics RNA Antisense Small nucleolar RNA Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics Cell Biology/Gene Expression 030304 developmental biology 0303 health sciences 030302 biochemistry & molecular biology Intron RNA Genetics and Genomics/Gene Expression DNA-Directed RNA Polymerases Telomere Non-coding RNA Introns Antisense RNA Cell biology lcsh:Genetics TRAMP complex Mutation RNA Interference Molecular Biology/mRNA Stability Research Article |
| Zdroj: | PLoS Genetics, 5 (7) PLoS Genetics PLoS Genetics, Vol 5, Iss 7, p e1000555 (2009) |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.3929/ethz-b-000019000 |
| Popis: | Trf4p and Trf5p are non-canonical poly(A) polymerases and are part of the heteromeric protein complexes TRAMP4 and TRAMP5 that promote the degradation of aberrant and short-lived RNA substrates by interacting with the nuclear exosome. To assess the level of functional redundancy between the paralogous Trf4 and Trf5 proteins and to investigate the role of the Trf4-dependent polyadenylation in vivo, we used DNA microarrays to compare gene expression of the wild-type yeast strain of S. cerevisiae with either that of trf4Δ or trf5Δ mutant strains or the trf4Δ mutant expressing the polyadenylation-defective Trf4(DADA) protein. We found little overlap between the sets of transcripts with altered expression in the trf4Δ or the trf5Δ mutants, suggesting that Trf4p and Trf5p target distinct groups of RNAs for degradation. Surprisingly, most RNAs the expression of which was altered by the trf4 deletion were restored to wild-type levels by overexpression of TRF4(DADA), showing that the polyadenylation activity of Trf4p is dispensable in vivo. Apart from previously reported Trf4p and Trf5p target RNAs, this analysis along with in vivo cross-linking and RNA immunopurification-chip experiments revealed that both the TRAMP4 and the TRAMP5 complexes stimulate the degradation of spliced-out introns via a mechanism that is independent of the polyadenylation activity of Trf4p. In addition, we show that disruption of trf4 causes severe shortening of telomeres suggesting that TRF4 functions in the maintenance of telomere length. Finally, our study demonstrates that TRF4, the exosome, and TRF5 participate in antisense RNA–mediated regulation of genes involved in phosphate metabolism. In conclusion, our results suggest that paralogous TRAMP complexes have distinct RNA selectivities with functional implications in RNA surveillance as well as other RNA–related processes. This indicates widespread and integrative functions of TRAMP complexes for the coordination of different gene expression regulatory processes. PLoS Genetics, 5 (7) ISSN:1553-7390 ISSN:1553-7404 |
| Databáze: | OpenAIRE |
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