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

V Runfola, S Sebastian, FJ Dilworth… - Journal of cell …, 2015 - journals.biologists.com
V Runfola, S Sebastian, FJ Dilworth, D Gabellini
Journal of cell science, 2015journals.biologists.com
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 …
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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