Format

Send to

Choose Destination
J Cell Sci. 2015 Feb 15;128(4):631-7. doi: 10.1242/jcs.161059. Epub 2015 Jan 20.

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

Author information

1
Dulbecco Telethon Institute and Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, Italy Università Vita-Salute San Raffaele, 20132 Milan, Italy.
2
The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada.
3
Dulbecco Telethon Institute and Division of Regenerative Medicine, San Raffaele Scientific Institute, 20132 Milan, Italy gabellini.davide@hsr.it.

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.

KEYWORDS:

Alternative splicing; Mef2; Muscle differentiation; Rbfox

PMID:
25609712
PMCID:
PMC4357529
DOI:
10.1242/jcs.161059
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center