miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy

EMBO Rep. 2011 Feb;12(2):136-41. doi: 10.1038/embor.2010.208. Epub 2011 Jan 7.

Abstract

Duchenne muscular dystrophy (DMD)--which is caused by mutations in the dystrophin gene-is one of the most severe myopathies. Among therapeutic strategies, exon skipping allows the rescue of dystrophin synthesis through the production of a shorter but functional messenger RNA. Here, we report the identification of a microRNA--miR-31--that represses dystrophin expression by targeting its 3' untranslated region. In human DMD myoblasts treated with exon skipping, we demonstrate that miR-31 inhibition increases dystrophin rescue. These results indicate that interfering with miR-31 activity can provide an ameliorating strategy for those DMD therapies that are aimed at efficiently recovering dystrophin synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Dystrophin / biosynthesis*
  • Dystrophin / genetics
  • Gene Expression Profiling
  • Humans
  • Mice
  • Mice, Inbred mdx
  • MicroRNAs / biosynthesis*
  • Muscular Dystrophy, Duchenne / metabolism*
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / therapy
  • Myotonia Congenita / metabolism
  • Myotonia Congenita / pathology
  • RNA Interference
  • RNA, Messenger / metabolism
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / metabolism

Substances

  • 3' Untranslated Regions
  • Dystrophin
  • MIRN31 microRNA, human
  • MicroRNAs
  • RNA, Messenger