The pivotal roles of TIA proteins in 5' splice-site selection of alu exons and across evolution
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- dc.contributor.author Gal-Mark, Nuritca
- dc.contributor.author Schwartz, Schragaca
- dc.contributor.author Ram, Orenca
- dc.contributor.author Eyras Jiménez, Eduardoca
- dc.contributor.author Ast, Gilca
- dc.date.accessioned 2016-05-02T14:06:58Z
- dc.date.available 2016-05-02T14:06:58Z
- dc.date.issued 2009
- dc.description.abstract More than 5% of alternatively spliced internal exons in the human genome are derived from Alu elements in a process termed exonization. Alus are comprised of two homologous arms separated by an internal polypyrimidine tract (PPT). In most exonizations, splice sites are selected from within the same arm. We hypothesized that the internal PPT may prevent selection of a splice site further downstream. Here, we demonstrate that this PPT enhanced the selection of an upstream 5' splice site (5'ss), even in the presence of a stronger 5'ss downstream. Deletion of this PPT shifted selection to the stronger downstream 5'ss. This enhancing effect depended on the strength of the downstream 5'ss, on the efficiency of base-pairing to U1 snRNA, and on the length of the PPT. This effect of the PPT was mediated by the binding of TIA proteins and was dependent on the distance between the PPT and the upstream 5'ss. A wide-scale evolutionary analysis of introns across 22 eukaryotes revealed an enrichment in PPTs within approximately 20 nt downstream of the 5'ss. For most metazoans, the strength of the 5'ss inversely correlated with the presence of a downstream PPT, indicative of the functional role of the PPT. Finally, we found that the proteins that mediate this effect, TIA and U1C, and in particular their functional domains, are highly conserved across evolution. Overall, these findings expand our understanding of the role of TIA1/TIAR proteins in enhancing recognition of exons, in general, and Alu exons, in particular.ca
- dc.description.sponsorship GA is supported by a grant from the Israel Science Foundation (1449/04), MOP Germany-Israel, GIF, and DIP. SS is a fellow of the Edmond J. Safra Bioinformatic Program at Tel Aviv University. OR is supported by EURASNET. EE is supported by the Catalan Institute for Research and Advanced Studies (ICREA) and by the BIO2008-01091 grant from the Spanish Ministry of Science.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Gal-Mark N, Schwartz S, Ram O, Eyras E, Ast G. The pivotal roles of TIA proteins in 5' splice-site selection of alu exons and across evolution. PLoS genetics. 2009;5(11):e1000717. DOI: 10.1371/journal.pgen.1000717ca
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1000717
- dc.identifier.issn 1553-7390
- dc.identifier.uri http://hdl.handle.net/10230/26231
- dc.language.iso engca
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS genetics. 2009;5(11):e1000717
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-01091
- dc.rights © 2009 Gal-Mark et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.other Biologia computacionalca
- dc.subject.other Proteïnesca
- dc.title The pivotal roles of TIA proteins in 5' splice-site selection of alu exons and across evolutionca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca