Rbfox2-coordinated alternative splicing of Mef2d and Rock2 controls myoblast fusion during myogenesis. Mol Cell 2014 Aug 21;55(4):592-603
Date
08/05/2014Pubmed ID
25087874Pubmed Central ID
PMC4142074DOI
10.1016/j.molcel.2014.06.035Scopus ID
2-s2.0-84906791713 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
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.
Author List
Singh RK, Xia Z, Bland CS, Kalsotra A, Scavuzzo MA, Curk T, Ule J, Li W, Cooper TAMESH terms used to index this publication - Major topics in bold
Alternative SplicingAnimals
COS Cells
Cell Line
Conserved Sequence
Gene Expression Regulation
HEK293 Cells
Humans
MEF2 Transcription Factors
Mice
Muscle Development
Myoblasts
Organ Specificity
Protein Isoforms
RNA
RNA-Binding Proteins
Sequence Analysis, RNA
rho-Associated Kinases
