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An alternative splicing event amplifies evolutionary differences between vertebrates

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dc.contributor.author Gueroussov, Serge
dc.contributor.author Gonatopoulos-Pournatzis, Thomas
dc.contributor.author Irimia, Manuel
dc.contributor.author Raj, Bushra
dc.contributor.author Lin, Zhen-Yuan
dc.contributor.author Gingras, Anne-Claude
dc.contributor.author Blencowe, Benjamin J.
dc.date.accessioned 2016-07-25T13:49:37Z
dc.date.available 2016-07-25T13:49:37Z
dc.date.issued 2015
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.aaa8381
dc.identifier.issn 0036-8075
dc.identifier.uri http://hdl.handle.net/10230/27120
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 systems
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/pdf
dc.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
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.
dc.subject.other Neurobiologia del desenvolupament
dc.subject.other Cél·lules mare embrionàries
dc.title An alternative splicing event amplifies evolutionary differences between vertebrates
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1126/science.aaa8381
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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