Widespread intron retention in mammals functionally tunes transcriptomes

Detalhes bibliográficos
Autor(a) principal: Braunschweig, Ulrich
Data de Publicação: 2014
Outros Autores: Barbosa-Morais, Nuno, Pan, Qun, Nachman, Emil N., Alipanahi, Babak, Gonatopoulos-Pournatzis, Thomas, Frey, Brendan, Irimia, Manuel, Blencowe, Benjamin J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/51322
Resumo: © 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/.
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spelling Widespread intron retention in mammals functionally tunes transcriptomes© 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/.Alternative 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.This 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.).Cold Spring Harbor Laboratory PressRepositório da Universidade de LisboaBraunschweig, UlrichBarbosa-Morais, NunoPan, QunNachman, Emil N.Alipanahi, BabakGonatopoulos-Pournatzis, ThomasFrey, BrendanIrimia, ManuelBlencowe, Benjamin J.2022-02-15T15:20:15Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51322engGenome Res. 2014 Nov;24(11):1774-17861088-905110.1101/gr.177790.1141549-5469info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:56Zoai:repositorio.ul.pt:10451/51322Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:37.371277Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Widespread intron retention in mammals functionally tunes transcriptomes
title Widespread intron retention in mammals functionally tunes transcriptomes
spellingShingle Widespread intron retention in mammals functionally tunes transcriptomes
Braunschweig, Ulrich
title_short Widespread intron retention in mammals functionally tunes transcriptomes
title_full Widespread intron retention in mammals functionally tunes transcriptomes
title_fullStr Widespread intron retention in mammals functionally tunes transcriptomes
title_full_unstemmed Widespread intron retention in mammals functionally tunes transcriptomes
title_sort Widespread intron retention in mammals functionally tunes transcriptomes
author Braunschweig, Ulrich
author_facet Braunschweig, Ulrich
Barbosa-Morais, Nuno
Pan, Qun
Nachman, Emil N.
Alipanahi, Babak
Gonatopoulos-Pournatzis, Thomas
Frey, Brendan
Irimia, Manuel
Blencowe, Benjamin J.
author_role author
author2 Barbosa-Morais, Nuno
Pan, Qun
Nachman, Emil N.
Alipanahi, Babak
Gonatopoulos-Pournatzis, Thomas
Frey, Brendan
Irimia, Manuel
Blencowe, Benjamin J.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Braunschweig, Ulrich
Barbosa-Morais, Nuno
Pan, Qun
Nachman, Emil N.
Alipanahi, Babak
Gonatopoulos-Pournatzis, Thomas
Frey, Brendan
Irimia, Manuel
Blencowe, Benjamin J.
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/.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2022-02-15T15:20:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/51322
url http://hdl.handle.net/10451/51322
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Genome Res. 2014 Nov;24(11):1774-1786
1088-9051
10.1101/gr.177790.114
1549-5469
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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