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Conserved functional antagonism of CELF 1 and MBNL proteins controls stem cell-specific alternative splicing in planarians

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Item Type:Article
Title:Conserved functional antagonism of CELF 1 and MBNL proteins controls stem cell-specific alternative splicing in planarians
Creators Name:Solana, J. and Irimia, M. and Ayoub, S. and Orejuela, M.R. and Zywitza, V. and Jens, M. and Tapial, J. and Ray, D. and Morris, Q.D. and Hughes, T.R. and Blencowe, B.J. and Rajewsky, N.
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 in animal stem cell regulation across metazoans.
Keywords:Alternative Splicing, Cell Differentiation, Cell Proliferation, Gene Expression Regulation, Gene Knockdown Techniques, RNA-Binding Proteins, Stem Cells, Animals, Planarians
Source:eLife
ISSN:2050-084X
Publisher:eLife Sciences Publications (U.K.)
Volume:5
Page Range:e16797
Date:9 August 2016
Official Publication:https://doi.org/10.7554/eLife.16797.001
PubMed:View item in PubMed

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