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

Valeria Runfola, Soji Sebastian, F. Jeffrey Dilworth, Davide Gabellini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)631-637
Number of pages7
JournalJournal of Cell Science
Volume128
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • Alternative splicing
  • Mef2
  • Muscle differentiation
  • Rbfox

ASJC Scopus subject areas

  • Cell Biology

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