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

RK Singh, Z Xia, CS Bland, A Kalsotra, MA Scavuzzo… - Molecular cell, 2014 - cell.com
Molecular cell, 2014cell.com
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 …
Summary
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.
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