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Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians

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dc.contributor.author Solana, Jordi
dc.contributor.author Irimia, Manuel
dc.contributor.author Ayoub, Salah
dc.contributor.author Rodriguez Orejuela, Marta
dc.contributor.author Zywitza, Vera
dc.contributor.author Jens, Marvin
dc.contributor.author Tapial Rodríguez, Javier, 1990-
dc.contributor.author Ray, Debashish
dc.contributor.author Morris, Quaid
dc.contributor.author Hughes, Timothy R.
dc.contributor.author Blencowe, Benjamin J.
dc.contributor.author Rajewsky, Nicolaus
dc.date.accessioned 2017-04-20T12:09:08Z
dc.date.available 2017-04-20T12:09:08Z
dc.date.issued 2016
dc.identifier.citation Solana J, Irimia M, Ayoub S, Rodriguez Orejuela M, Zywitza V, Jens M et al. Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians. eLife. 2016;5:e16797. DOI: 10.7554/eLife.16797
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/30858
dc.description.abstract In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.
dc.description.sponsorship We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and BFU2014-55076-P to MI and a CIHR Operating Grant MOP-125894 to QDM and TRH.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher eLife
dc.relation.ispartof eLife. 2016;5:e16797
dc.rights © Copyright Solana et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.7554/eLife.16797
dc.subject.keyword Alternative splicing
dc.subject.keyword Planaria
dc.subject.keyword Post-transcriptional gene regulation
dc.subject.keyword Regeneration
dc.subject.keyword Schmidtea mediterranea
dc.subject.keyword Stem cells
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
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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