Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis

Ravi K. Singh, Zheng Xia, Christopher S. Bland, Auinash Kalsotra, Marissa A. Scavuzzo, Tomaz Curk, Jernej Ule, Wei Li, Thomas A. Cooper

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Alternative splicing plays important regulatory roles during periods of physiological change. During development, a large number of genes coordinately express protein isoform transitions regulated by alternative splicing; however, the mechanisms that coordinate splicing and the functional integration of the resultant tissue-specific protein isoforms are typically unknown. Here we show that the conserved Rbfox2 RNA binding protein regulates 30% of the splicing transitions observed during myogenesis and is required for the specific step of myoblast fusion. Integration of Rbfox2-dependent splicing outcomes from RNA-seq with Rbfox2 iCLIP data identified Mef2d and Rock2 as Rbfox2 splicing targets. Restored activities of Mef2d and Rock2 rescued myoblast fusion in Rbfox2-depleted cultures, demonstrating functional cooperation of protein isoforms generated by coordinated alterative splicing. The results demonstrate that coordinated alternative splicing by a single RNA binding protein modulates transcription (Mef2d) and cell signaling (Rock2) programs to drive tissue-specific functions (cell fusion) to promote a developmental transition.

Original languageEnglish (US)
Pages (from-to)592-603
Number of pages12
JournalMolecular Cell
Volume55
Issue number4
DOIs
StatePublished - Aug 21 2014
Externally publishedYes

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Muscle Development
Myoblasts
Alternative Splicing
Protein Isoforms
RNA-Binding Proteins
RNA Splicing
Cell Fusion
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Singh, R. K., Xia, Z., Bland, C. S., Kalsotra, A., Scavuzzo, M. A., Curk, T., ... Cooper, T. A. (2014). Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis. Molecular Cell, 55(4), 592-603. https://doi.org/10.1016/j.molcel.2014.06.035

Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis. / Singh, Ravi K.; Xia, Zheng; Bland, Christopher S.; Kalsotra, Auinash; Scavuzzo, Marissa A.; Curk, Tomaz; Ule, Jernej; Li, Wei; Cooper, Thomas A.

In: Molecular Cell, Vol. 55, No. 4, 21.08.2014, p. 592-603.

Research output: Contribution to journalArticle

Singh, RK, Xia, Z, Bland, CS, Kalsotra, A, Scavuzzo, MA, Curk, T, Ule, J, Li, W & Cooper, TA 2014, 'Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis', Molecular Cell, vol. 55, no. 4, pp. 592-603. https://doi.org/10.1016/j.molcel.2014.06.035
Singh, Ravi K. ; Xia, Zheng ; Bland, Christopher S. ; Kalsotra, Auinash ; Scavuzzo, Marissa A. ; Curk, Tomaz ; Ule, Jernej ; Li, Wei ; Cooper, Thomas A. / Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis. In: Molecular Cell. 2014 ; Vol. 55, No. 4. pp. 592-603.
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