In vitro evidence suggests that miR-133a-mediated regulation of uncoupling protein 2 (UCP2) is an indispensable step in myogenic differentiation

J Biol Chem. 2009 Feb 20;284(8):5362-9. doi: 10.1074/jbc.M807523200. Epub 2008 Dec 10.


UCP2 and UCP3, two novel uncoupling proteins, are important regulators of energy expenditure and thermogenesis in various organisms. The striking disparity between UCP2 mRNA and protein levels in muscle tissues prompted initial speculation that microRNAs are implicated in the regulatory pathway of UCP2. We found, for the first time, that the repression of UCP2 expression in cardiac and skeletal muscle resulted from its targeting by a muscle-specific microRNA, miR-133a. Moreover, our findings illustrate a novel function of UCP2 as a brake for muscle development. We also show that MyoD can remove the braking role of UCP2 via direct up-regulation of miR-133a during myogenic differentiation. Taken together, our current work delineates a novel regulatory network employing MyoD, microRNA, and uncoupling proteins to fine-tune the balance between muscle differentiation and proliferation during myogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Line, Tumor
  • Ion Channels / biosynthesis*
  • Ion Channels / genetics
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / genetics
  • Muscle Development / physiology*
  • Muscle, Skeletal / metabolism*
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myocardium / metabolism*
  • Uncoupling Protein 2
  • Uncoupling Protein 3


  • Ion Channels
  • MicroRNAs
  • Mitochondrial Proteins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Ucp2 protein, mouse
  • Ucp3 protein, mouse
  • Uncoupling Protein 2
  • Uncoupling Protein 3