Misregulation of alternative splicing of BIN1 leads to T-tubule alterations and muscle weakness in myotonic dystrophy

ABSTRACT: Myotonic dystrophes (DM), the most common adult muscular dystrophy, are the first recognized examples of RNA-mediated diseases in which expression of mutant RNAs containing expanded CUG or CCUG repeats interfere with the splicing of other mRNAs. Using whole-genome microarrays, we found that alternative splicing of the BIN1 mRNA is altered in DM skeletal muscle tissues, resulting in the expression of an inactive form of BIN1 deprived of phosphoinositide-binding and membrane-tubulating activities. BIN1 is involved in tubular invaginations of the plasma membrane and is essential for biogenesis of the muscle T-tubules, which are specialized skeletal muscle membrane structures essential to correct excitation-contraction (E-C) coupling. Mutations in the BIN1 gene cause centronuclear myopathy (CN

ORGANISM(S): Homo sapiens

SUBMITTER: Doulaye Dembele 

PROVIDER: E-GEOD-21795 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress