Solana, JordiIrimia Martínez, ManuelAyoub, SalahRodriguez Orejuela, MartaZywitza, VeraJens, MarvinTapial Rodríguez, Javier, 1990-Ray, DebashishMorris, QuaidHughes, Timothy R.Blencowe, Benjamin J.Rajewsky, Nicolaus2017-04-202017-04-202016Solana 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.167972050-084Xhttp://hdl.handle.net/10230/30858In 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.16797Alternative splicingPlanariaPost-transcriptional gene regulationRegenerationSchmidtea mediterraneaStem cellsinfo:eu-repo/semantics/openAccess