A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA

Cell. 2011 Oct 14;147(2):358-69. doi: 10.1016/j.cell.2011.09.028.


Recently, a new regulatory circuitry has been identified in which RNAs can crosstalk with each other by competing for shared microRNAs. Such competing endogenous RNAs (ceRNAs) regulate the distribution of miRNA molecules on their targets and thereby impose an additional level of post-transcriptional regulation. Here we identify a muscle-specific long noncoding RNA, linc-MD1, which governs the time of muscle differentiation by acting as a ceRNA in mouse and human myoblasts. Downregulation or overexpression of linc-MD1 correlate with retardation or anticipation of the muscle differentiation program, respectively. We show that linc-MD1 "sponges" miR-133 and miR-133 [corrected] to regulate the expression of MAML1 and MEF2C, transcription factors that activate muscle-specific gene expression. Finally, we demonstrate that linc-MD1 exerts the same control over differentiation timing in human myoblasts, and that its levels are strongly reduced in Duchenne muscle cells. We conclude that the ceRNA network plays an important role in muscle differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Developmental*
  • Humans
  • MADS Domain Proteins / genetics
  • MEF2 Transcription Factors
  • Mice
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Muscle Development*
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / embryology
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Myoblasts / metabolism
  • Myogenic Regulatory Factors / genetics
  • Nuclear Proteins / genetics
  • RNA Processing, Post-Transcriptional
  • RNA, Long Noncoding
  • RNA, Untranslated / metabolism*
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • MADS Domain Proteins
  • MAML1 protein, human
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • MIRN206 microRNA, human
  • Maml1 protein, mouse
  • Mef2c protein, mouse
  • MicroRNAs
  • Myogenic Regulatory Factors
  • Nuclear Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Transcription Factors
  • linc-md1 long noncoding RNA, human
  • long noncoding RNA, linc-MD1, mouse