Myotonic Dystrophy (DM), the most common muscular dystrophy in adults, is an RNA gain-of-function disease caused by expanded CUG or CCUG repeats that sequester the RNA binding protein MBNL1. MBNL1 is now shown to regulate pre-miR-1 processing. In DM patients, MBNL1 levels are low and another protein binds to pre-miR-1 and promotes its subsequent uridylation, making it resistant to Dicer cleavage. This results in lower amounts of miR-1 and increased levels of its targets, GJA1 and CACNA1C, that encode the main calcium and gap junction channels in the heart, respectively. Thus their misregulation may contribute to the cardiac dysfunctions observed in DM patients.
- Frédérique Rau
- Fernande Freyermuth
- Nicolas Charlet-Berguerand
