1. Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required for muscle differentiation.
- Author
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Runfola V, Sebastian S, Dilworth FJ, and Gabellini D
- Subjects
- Alternative Splicing physiology, Animals, Cell Line, MEF2 Transcription Factors genetics, Mice, Muscle Development genetics, Muscle Development physiology, Muscles cytology, Protein Isoforms metabolism, RNA Interference, RNA Splicing Factors, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering, Alternative Splicing genetics, Cell Differentiation genetics, RNA-Binding Proteins genetics
- 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., (© 2015. Published by The Company of Biologists Ltd.)
- Published
- 2015
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