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Widespread intron retention in mammals functionally tunes transcriptomes

2014Journal article Open access
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dc.contributor.authorBraunschweig, Ulrich
dc.contributor.authorBarbosa-Morais, Nuno
dc.contributor.authorPan, Qun
dc.contributor.authorNachman, Emil N.
dc.contributor.authorAlipanahi, Babak
dc.contributor.authorGonatopoulos-Pournatzis, Thomas
dc.contributor.authorFrey, Brendan
dc.contributor.authorIrimia, Manuel
dc.contributor.authorBlencowe, Benjamin J.
dc.date.accessioned2022-02-15T15:20:15Z
dc.date.available2022-02-15T15:20:15Z
dc.date.issued2014
dc.description© 2014 Braunschweig et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.pt_PT
dc.description.abstractAlternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)(+) RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an "IR code" reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This "transcriptome tuning" function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.pt_PT
dc.description.sponsorshipThis work was supported by grants from the Canadian Institutes of Health Research and Canadian Cancer Society (B.J.B.); EMBO long-term fellowships (U.B. and T.G.-P.); Human Frontier Science Program Organization long-term fellowships (U.B. and M.I.); an OSCI fellowship (T.G.-P.); CIHR postdoctoral and Marie Curie IOF fellowships (N.L.B.-M.); and an NSERC studentship (E.N.).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGenome Res. 2014 Nov;24(11):1774-1786pt_PT
dc.identifier.doi10.1101/gr.177790.114pt_PT
dc.identifier.eissn1549-5469
dc.identifier.issn1088-9051
dc.identifier.urihttp://hdl.handle.net/10451/51322
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCold Spring Harbor Laboratory Presspt_PT
dc.relation.publisherversionhttps://genome.cshlp.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.titleWidespread intron retention in mammals functionally tunes transcriptomespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1786pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1774pt_PT
oaire.citation.titleGenome Researchpt_PT
oaire.citation.volume24pt_PT
person.familyNameBARBOSA MORAIS
person.givenNameNUNO LUÍS
person.identifierI-2743-2013
person.identifier.ciencia-id5C19-CA77-A74D
person.identifier.orcid0000-0002-1215-0538
person.identifier.scopus-author-id6507555084
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7ebfc1e4-56dd-40a2-bb4c-5086cd039ee2
relation.isAuthorOfPublication.latestForDiscovery7ebfc1e4-56dd-40a2-bb4c-5086cd039ee2

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