TY - JOUR
T1 - Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required for muscle differentiation
AU - Runfola, Valeria
AU - Sebastian, Soji
AU - Dilworth, F. Jeffrey
AU - Gabellini, Davide
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Mef2
KW - Muscle differentiation
KW - Rbfox
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U2 - 10.1242/jcs.161059
DO - 10.1242/jcs.161059
M3 - Article
AN - SCOPUS:84924709717
VL - 128
SP - 631
EP - 637
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 4
ER -