Decoding muscle alternative splicing.

Muscle was one of the first tissues in which alternative splicing was widely observed. Cloning and sequencing of muscle-derived cDNAs in the early 1980's revealed that many of the abundant contractile proteins arise by alternative splicing of genes that are more widely expressed. Consequently alternative splicing events in contractile protein genes have long been used as models to dissect the mechanisms of alternative splicing. Transcriptomic and computational analyses have complemented traditional molecular analyses of alternative splicing in muscle and other tissues, illuminating the general underlying principles of coregulated splicing programs. This has culminated in the first attempt to computationally predict tissue-specific changes in splicing. Investigations of myotonic dystrophy (DM), in which CUG expansion RNA leads to misregulated splicing in muscle, have enhanced our understanding of developmentally regulated splicing and led to the development of promising therapeutic strategies based on targeting the toxic RNA repeats.