Antagonistic role of MBNL1 and LIN28 promotes specific alteration of pre-miR-1 processing and is associated with heart defects in DM

ABSTRACT: Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, is caused by the expression of expanded CUG repeats, which sequester the MBNL1 RNA binding protein. Cardiac involvement, which is characterized by conduction defects and arrhythmias, is the second cause of death of DM1 patients. Down-expression of miR-1 in mice leads to cardiac conduction disturbances and to arrhythmias. Here, we show that miR-1 expression is decreased in DM1 hearts, due to a mis-regulation of the processing of pre-miR-1. MBNL1 binds to UGC motifs located within the pre-miR-1 loop and competes binding of LIN28, which promotes uridylation and blocks pre-miR-1 processing. Finally and consistent with a down-regulation of miR-1, known, GJA1, and novel, CACNA1C, targets of miR-1 are increased in DM1

ORGANISM(S): Homo sapiens

SUBMITTER: Doulaye Dembele 

PROVIDER: E-GEOD-24109 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress