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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, Manuel
dc.date.accessioned 2021-05-03T07:45:18Z
dc.date.available 2021-05-03T07:45:18Z
dc.date.issued 2017
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.issn 1088-9051
dc.identifier.uri http://hdl.handle.net/10230/47278
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.language.iso eng
dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
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.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.identifier.doi http://dx.doi.org/10.1101/gr.220962.117
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/637591
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55076-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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