Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians
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- dc.contributor.author Solana, Jordica
- dc.contributor.author Irimia Martínez, Manuelca
- dc.contributor.author Ayoub, Salahca
- dc.contributor.author Rodriguez Orejuela, Martaca
- dc.contributor.author Zywitza, Veraca
- dc.contributor.author Jens, Marvinca
- dc.contributor.author Tapial Rodríguez, Javier, 1990-ca
- dc.contributor.author Ray, Debashishca
- dc.contributor.author Morris, Quaidca
- dc.contributor.author Hughes, Timothy R.ca
- dc.contributor.author Blencowe, Benjamin J.ca
- dc.contributor.author Rajewsky, Nicolausca
- dc.date.accessioned 2017-04-20T12:09:08Z
- dc.date.available 2017-04-20T12:09:08Z
- dc.date.issued 2016
- 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/pdfca
- 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.doi http://dx.doi.org/10.7554/eLife.16797
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/30858
- dc.language.iso eng
- dc.publisher eLifeca
- dc.relation.ispartof eLife. 2016;5:e16797
- 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 © 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.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- 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.title Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planariansca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion