Rbfox Proteins Regulate Tissue-specific Alternative Splicing of Mef2D Required for Muscle Differentiation

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2015 Jan 23

PMID 25609712

Citations 33

Authors

Valeria Runfola

Soji Sebastian

F Jeffrey Dilworth

Davide Gabellini

Affiliations

Soon will be listed here.

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.

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