An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms

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  • dc.contributor.author Tapial Rodríguez, Javier, 1990-
  • dc.contributor.author Ha, Kevin C. H.
  • dc.contributor.author Sterne-Weiler, Thimothy
  • dc.contributor.author Gohr, André
  • dc.contributor.author Braunschweig, Ulrich
  • dc.contributor.author Hermoso Pulido, Antonio
  • dc.contributor.author Quesnel-Vallières, Mathieu
  • dc.contributor.author Permanyer, Jon
  • dc.contributor.author Sodaei, Reza, 1988-
  • dc.contributor.author Marquez, Yamile
  • dc.contributor.author Cozzuto, Luca
  • dc.contributor.author Wang, Xinchen
  • dc.contributor.author Gómez-Velázquez, Melisa
  • dc.contributor.author Rayon, Teresa
  • dc.contributor.author Manzanares, Miguel
  • dc.contributor.author Ponomarenko, Julia
  • dc.contributor.author Blencowe, Benjamin J.
  • dc.contributor.author Irimia Martínez, Manuel
  • dc.date.accessioned 2021-05-03T07:45:18Z
  • dc.date.available 2021-05-03T07:45:18Z
  • dc.date.issued 2017
  • dc.description.abstract Alternative splicing (AS) generates remarkable regulatory and proteomic complexity in metazoans. However, the functions of most AS events are not known, and programs of regulated splicing remain to be identified. To address these challenges, we describe the Vertebrate Alternative Splicing and Transcription Database (VastDB), the largest resource of genome-wide, quantitative profiles of AS events assembled to date. VastDB provides readily accessible quantitative information on the inclusion levels and functional associations of AS events detected in RNA-seq data from diverse vertebrate cell and tissue types, as well as developmental stages. The VastDB profiles reveal extensive new intergenic and intragenic regulatory relationships among different classes of AS and previously unknown and conserved landscapes of tissue-regulated exons. Contrary to recent reports concluding that nearly all human genes express a single major isoform, VastDB provides evidence that at least 48% of multiexonic protein-coding genes express multiple splice variants that are highly regulated in a cell/tissue-specific manner, and that >18% of genes simultaneously express multiple major isoforms across diverse cell and tissue types. Isoforms encoded by the latter set of genes are generally coexpressed in the same cells and are often engaged by translating ribosomes. Moreover, they are encoded by genes that are significantly enriched in functions associated with transcriptional control, implying they may have an important and wide-ranging role in controlling cellular activities. VastDB thus provides an unprecedented resource for investigations of AS function and regulation.
  • dc.description.sponsorship This work has been supported by grants from the European Research Council (ERC-StG-LS2-637591 to M.I.), the Spanish Ministry of Economy and Competitiveness (Centro de Excelencia Severo Ochoa 2013–2017, SEV-2012-0208 to the CRG, SEV-2015-0505 to the CNIC, and BFU2014-55076-P to M.I.). J.T. holds a FPI Severo Ochoa fellowship and was supported by Grant SVP-2014-068315. K.C.H. was supported by an Ontario Graduate Scholarship and a CIHR Frederick Banting and Charles Best Canada Graduate Doctoral Award. Y.M. holds an EMBO LTF fellowship
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Tapial J, Ha KCH, Sterne-Weiler T, Gohr A, Braunschweig U, Hermoso-Pulido, A et al. An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms. Genome Res. 2017 Oct;27(10):1759-1768. DOI: 10.1101/gr.220962.117
  • dc.identifier.doi http://dx.doi.org/10.1101/gr.220962.117
  • dc.identifier.issn 1088-9051
  • dc.identifier.uri http://hdl.handle.net/10230/47278
  • dc.language.iso eng
  • dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/637591
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55076-P
  • dc.rights © 2017 Tapial et al. 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/
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Genòmica
  • dc.subject.other Proteïnes
  • dc.title An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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