Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a CTG microsatellite expansion (CTG^exp) disorder caused by expression of CUG^exp RNAs. These mutant RNAs alter the activities of RNA processing factors, including MBNL proteins, leading to re-expression of fetal isoforms in adult tissues and DM1 pathology. While this pathogenesis model accounts for adult-onset disease, the molecular basis of congenital DM (CDM) is unknown. Here, we test the hypothesis that disruption of developmentally regulated RNA alternative processing pathways contributes to CDM disease. We identify prominent alternative splicing and polyadenylation abnormalities in infant CDM muscle, and, although most are also misregulated in adult-onset DM1, dysregulation is significantly more severe in CDM. Furthermore, analys

SUBMITTER: Thomas JD 

PROVIDER: S-EPMC5538435 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature