Missplicing of the RNA of the BIN1 gene is associated with improper muscle activity in a common form of muscular dystrophy, called myotonic dystrophy. These findings, reported online this week in Nature Medicine, identify a new mechanism that explains an important aspect of this disease.
Myotonic dystrophy is characterized by improper muscle activity, or myotonia, and muscle wasting. The disease is caused by mutations in certain genes that result in an expansion of tri-nucleotide repeats in their corresponding RNAs. These repeated nucleotide sequences then sequester important RNA processing enzymes that result in missplicing of the RNA of other genes.
Nicolas Charlet-Berguerand and his colleagues find that one of the RNAs affected is for the gene BIN1. BIN1 is known to be critical in the formation of a membrane structure in skeletal muscle cells that allows for the proper coupling of excitation and contraction of the muscles. Missplicing of BIN1 results in the expression of a defective BIN1 isoform such that this membrane structure and excitation-contraction coupling is defective, likely explaining the myotonia.