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Article: Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing

TitleCotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicing
Authors
Issue Date2014
PublisherOxford University Press. The Journal's web site is located at http://nar.oxfordjournals.org/
Citation
Nucleic Acids Research, 2014, v. 42 n. 1, p. 643-660 How to Cite?
AbstractMost unwanted RNA transcripts in the nucleus of eukaryotic cells, such as splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts, including spliced-out introns, are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. However, it remains unclear when spliced-out introns are recognized by TRAMP, and whether TRAMP may have any potential roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is cotranscriptionally recruited to nascent RNA transcripts, with particular enrichment at intronic sequences. Deletion of TRAMP components led to further accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We also uncovered new genetic and physical interactions between TRAMP and several splicing factors, and further showed that TRAMP is required for optimal recruitment of the splicing factor Msl5p. Our study provided the first evidence that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe mechanism to ensure the cotranscriptional recruitment of TRAMP before or during splicing to prepare for the subsequent targeting of spliced-out introns to rapid degradation by the nuclear exosome.
Persistent Identifierhttp://hdl.handle.net/10722/194670
ISSN
2015 Impact Factor: 9.202
2015 SCImago Journal Rankings: 7.458
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKong, KYen_US
dc.contributor.authorTang, VHMen_US
dc.contributor.authorPan, Ken_US
dc.contributor.authorHuang, Zen_US
dc.contributor.authorLee, THJen_US
dc.contributor.authorHinnebusch, Aen_US
dc.contributor.authorJin, Den_US
dc.contributor.authorWong, CMen_US
dc.date.accessioned2014-02-17T02:02:24Z-
dc.date.available2014-02-17T02:02:24Z-
dc.date.issued2014en_US
dc.identifier.citationNucleic Acids Research, 2014, v. 42 n. 1, p. 643-660en_US
dc.identifier.issn0305-1048en_US
dc.identifier.urihttp://hdl.handle.net/10722/194670-
dc.description.abstractMost unwanted RNA transcripts in the nucleus of eukaryotic cells, such as splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts, including spliced-out introns, are first recognized by the nuclear exosome cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent nuclear-exosome-mediated degradation. However, it remains unclear when spliced-out introns are recognized by TRAMP, and whether TRAMP may have any potential roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is cotranscriptionally recruited to nascent RNA transcripts, with particular enrichment at intronic sequences. Deletion of TRAMP components led to further accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We also uncovered new genetic and physical interactions between TRAMP and several splicing factors, and further showed that TRAMP is required for optimal recruitment of the splicing factor Msl5p. Our study provided the first evidence that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe mechanism to ensure the cotranscriptional recruitment of TRAMP before or during splicing to prepare for the subsequent targeting of spliced-out introns to rapid degradation by the nuclear exosome.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://nar.oxfordjournals.org/en_US
dc.relation.ispartofNucleic Acids Researchen_US
dc.titleCotranscriptional recruitment of yeast TRAMP complex to intronic sequences promotes optimal pre-mRNA splicingen_US
dc.typeArticleen_US
dc.identifier.emailTang, VHM: tanghmv@hku.hken_US
dc.identifier.emailPan, K: pankewu@hku.hken_US
dc.identifier.emailJin, D: dyjin@hku.hken_US
dc.identifier.emailWong, CM: wispwong@hku.hken_US
dc.identifier.authorityJin, D=rp00452en_US
dc.identifier.authorityWong, CM=rp01489en_US
dc.identifier.doi10.1093/nar/gkt888en_US
dc.identifier.pmid24097436en_US
dc.identifier.pmcidPMC3874199en_US
dc.identifier.hkuros227780en_US
dc.identifier.volume42en_US
dc.identifier.issue1-
dc.identifier.spage643en_US
dc.identifier.epage660en_US
dc.identifier.isiWOS:000331136000057-
dc.publisher.placeUnited Kingdomen_US

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