Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis genes.

ABSTRACT: Myotonic dystrophies (DM1-2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3'UTR of the DMPK gene and CCTG repeats in the first intron of the CNBP gene, respectively. Mutant RNAs containing expanded repeats are retained in the cell nucleus, where they sequester nuclear factors and cause alterations in RNA metabolism. However, for unknown reasons, DM1 is more severe than DM2. To study the differences and similarities in the pathogenesis of DM1 and DM2, we generated model flies by expressing pure expanded CUG ([250]×) or CCUG ([1100]×) repeats, respectively, and compared them with control flies expressing either 20 repeat units or GFP. We observed surprisingly severe muscle redu

SUBMITTER: Cerro-Herreros E 

PROVIDER: S-EPMC5460254 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature