期刊
MOLECULAR CELL
卷 55, 期 4, 页码 592-603出版社
CELL PRESS
DOI: 10.1016/j.molcel.2014.06.035
关键词
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资金
- American Heart Association [12POST11770017, 11SDG4980011]
- Myotonic Dystrophy Foundation
- Ford Foundation Predoctoral Diversity Fellowship
- Baylor Research Advocates for Student Scientists (BRASS)
- BCM [AI036211, CA125123, RR024574, HD007495, DK56338, P30 CA125123]
- National Institutes of Health [R01HG007538, R01HL045565, R01AR060733, R01AR045653]
- Muscular Dystrophy Association
- Medical Research Council [MC_U105185858] Funding Source: researchfish
- MRC [MC_U105185858] Funding Source: UKRI
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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