An alternative splicing event amplifies evolutionary differences between vertebrates

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Gueroussov, Sergeca
• dc.contributor.author Gonatopoulos-Pournatzis, Thomasca
• dc.contributor.author Irimia Martínez, Manuelca
• dc.contributor.author Raj, Bushraca
• dc.contributor.author Lin, Zhen-Yuanca
• dc.contributor.author Gingras, Anne-Claudeca
• dc.contributor.author Blencowe, Benjamin J.ca
• dc.date.accessioned 2016-07-25T13:49:37Z
• dc.date.available 2016-07-25T13:49:37Z
• dc.date.issued 2015
• dc.description.abstract Alternative splicing (AS) generates extensive transcriptomic and proteomic complexity. However, the functions of species- and lineage-specific splice variants are largely unknown. Here we show that mammalian-specific skipping of polypyrimidine tract-binding protein 1 (PTBP1) exon 9 alters the splicing regulatory activities of PTBP1 and affects the inclusion levels of numerous exons. During neurogenesis, skipping of exon 9 reduces PTBP1 repressive activity so as to facilitate activation of a brain-specific AS program. Engineered skipping of the orthologous exon in chicken cells induces a large number of mammalian-like AS changes in PTBP1 target exons. These results thus reveal that a single exon-skipping event in an RNA binding regulator directs numerous AS changes between species. Our results further suggest that these changes contributed to evolutionary differences in the formation of vertebrate nervous systemsca
• dc.description.sponsorship SG is supported by an NSERC Alexander Graham Bell Studentship, TGP is supported by fellowships from EMBO and OSCI, and MI was supported by a LTF from the Human Frontiers Science Program Organization. This research was supported by grants from the CIHR to BJB and A-C.G. BJB holds the Banbury Chair of Medical Research at the University of Toronto. Data presented in this manuscript is archived in the gene Gene Expression Omnibus (GEO) under accession number GSE69656.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Gueroussov S, Gonatopoulos-Pournatzis T, Irimia M, Raj B, Lin ZY, Gingras AC et al. An alternative splicing event amplifies evolutionary differences between vertebrates. Science. 2015; 349(6250): 868-873. DOI 10.1126/science.aaa8381ca
• dc.identifier.doi http://dx.doi.org/10.1126/science.aaa8381
• dc.identifier.issn 0036-8075
• dc.identifier.uri http://hdl.handle.net/10230/27120
• dc.language.iso engca
• dc.publisher American Association for the Advancement of Science (AAAS)ca
• dc.relation.ispartof Science. 2015; 349(6250): 868-87
• dc.rights This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 349 in August 21 of 2015, DOI: 10.1126/science.aaa8381.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Neurobiologia del desenvolupamentca
• dc.subject.other Cél·lules mare embrionàriesca
• dc.title An alternative splicing event amplifies evolutionary differences between vertebratesca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca