Genome-wide association between branch point properties and alternative splicing

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Corvelo, Andréca
  • dc.contributor.author Hallegger, Martinaca
  • dc.contributor.author Smith, Christopher, W. J.ca
  • dc.contributor.author Eyras Jiménez, Eduardoca
  • dc.date.accessioned 2015-04-17T07:07:47Z
  • dc.date.available 2015-04-17T07:07:47Z
  • dc.date.issued 2010ca
  • dc.description.abstract The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3′ end of introns, with distance to the 3′ splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models.en
  • dc.description.sponsorship AC received support from the Graduate Program in Areas of Basic and Applied Biology (GABBA) and funding from the Portuguese Foundation for Science and Technology (ref. SFRH/BD/15240/2004). EE is supported by the Catalan Institution of Research and Advanced Studies (ICREA). This work was supported by the grant BIO2008-01091 from the Spanish Ministry of Science (EE) and by the project EURASNET-LSHG-CT-2005-518238 from the European Commission (EE & CWJS) and by Wellcome Trust programme 077877 (CWJS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Corvelo A, Hallegger M, Smith CWJ, Eyras E. Genome-wide association between branch point properties and alternative splicing. PLoS Computational Biology. 2010;6(11):e1001016. DOI: 10.1371/journal.pcbi.1001016ca
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1001016
  • dc.identifier.issn 1553-734Xca
  • dc.identifier.uri http://hdl.handle.net/10230/23433
  • dc.language.iso engca
  • dc.publisher Public Library of Science (PLoS)ca
  • dc.relation.ispartof PLoS Computational Biology. 2010;6(11):e1001016
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/518238ca
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-01091
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/077877
  • dc.rights © Corvelo A, Hallegger M, Smith CWJ, Eyras E. This is an Open Access article distributed under the terms of the Creative Commons Attribution...(CC BY) (http://creativecommons.org/licenses/by/2.5/).ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/2.5/
  • dc.subject.other Genètica -- Regulacióca
  • dc.subject.other Genòmicaca
  • dc.title Genome-wide association between branch point properties and alternative splicingen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

Col·leccions

Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)