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Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required for muscle differentiation.

ABSTRACT: Among the Mef2 family of transcription factors, Mef2D is unique in that it undergoes tissue-specific splicing to generate an isoform that is essential for muscle differentiation. However, the mechanisms mediating this muscle-specific processing of Mef2D remain unknown. Using bioinformatics, we identified Rbfox proteins as putative modulators of Mef2D muscle-specific splicing. Accordingly, we found direct and specific Rbfox1 and Rbfox2 binding to Mef2D pre-mRNA in vivo. Gain- and loss-of-function experiments demonstrated that Rbfox1 and Rbfox2 cooperate in promoting Mef2D splicing and subsequent myogenesis. Thus, our findings reveal a new role for Rbfox proteins in regulating myogenesis through activation of essential muscle-specific splicing events.

SUBMITTER: Runfola V

PROVIDER: S-EPMC4357529 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required for muscle differentiation.

Runfola Valeria V Sebastian Soji S Dilworth F Jeffrey FJ Gabellini Davide D

Journal of cell science 20150120 4

Among the Mef2 family of transcription factors, Mef2D is unique in that it undergoes tissue-specific splicing to generate an isoform that is essential for muscle differentiation. However, the mechanisms mediating this muscle-specific processing of Mef2D remain unknown. Using bioinformatics, we identified Rbfox proteins as putative modulators of Mef2D muscle-specific splicing. Accordingly, we found direct and specific Rbfox1 and Rbfox2 binding to Mef2D pre-mRNA in vivo. Gain- and loss-of-function ...[more]

PMID: 25609712

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