miR-186 inhibits muscle cell differentiation through myogenin regulation

Antonis Antoniou, Nikolaos P Mastroyiannopoulos, James B Uney, Leonidas A Phylactou

Research output: Contribution to journalArticle (Academic Journal)peer-review

44 Citations (Scopus)

Abstract

The complex process of skeletal muscle differentiation is organized by the myogenic regulatory factors (MRFs), Myf5, MyoD, Myf6, and myogenin, where myogenin plays a critical role in the regulation of the final stage of muscle differentiation. In an effort to investigate the role microRNAs (miRNAs) play in regulating myogenin, a bioinformatics approach was used and six miRNAs (miR-182, miR-186, miR-135, miR-491, miR-329, and miR-96) were predicted to bind the myogenin 3'-untranslated region (UTR). However, luciferase assays showed only miR-186 inhibited translation and 3'-UTR mutagenesis analysis confirmed this interaction was specific. Interestingly, the expression of miR-186 mirrored that of its host gene, ZRANB2, during development. Functional studies demonstrated that miR-186 overexpression inhibited the differentiation of C2C12 and primary muscle cells. Our findings therefore identify miR-186 as a novel regulator of myogenic differentiation.

Original languageEnglish
Pages (from-to)3923-35
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number7
DOIs
Publication statusPublished - 14 Feb 2014

Keywords

  • 3' Untranslated Regions
  • Animals
  • Cell Differentiation
  • Cell Line
  • Mice
  • MicroRNAs
  • Muscle, Skeletal
  • Myogenin
  • RNA-Binding Proteins

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