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MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206

Miriam I Rosenberg1, Sara A Georges, Amy Asawachaicharn

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

The Journal of Cell Biology
|October 13, 2006
PubMed

Insights

MyoD transcription factor activates muscle genes and suppresses others. It induces miR-206 microRNA, which targets Fstl1 and Utrn RNA, repressing their expression during skeletal muscle differentiation.

Area of Science:

  • Molecular Biology
  • Cellular Differentiation
  • Gene Regulation

Background:

  • Cell differentiation involves activating specific genes and suppressing precursor genes.
  • Utrophin (Utrn) expression is suppressed during skeletal muscle differentiation, replaced by dystrophin.
  • The MyoD transcription factor plays a key role in skeletal muscle gene regulation.

Purpose of the Study:

  • To investigate the mechanism of MyoD-mediated gene suppression.
  • To identify genes suppressed by MyoD during fibroblast-to-muscle conversion.
  • To understand the role of microRNAs in MyoD-induced gene repression.

Main Methods:

  • Investigated MyoD-mediated suppression of follistatin-like 1 (Fstl1) and Utrophin (Utrn) genes.
  • Analyzed the direct activation of a muscle-specific microRNA (miRNA) by MyoD.
  • Utilized RNA targeting sequences to demonstrate miRNA-mediated gene suppression.

Main Results:

  • MyoD directly activates the expression of miR-206.
  • miR-206 targets sequences within Fstl1 and Utrn RNA.
  • These targeted sequences are sufficient to suppress gene expression in the presence of miR-206.

Conclusions:

  • MyoD induces muscle-specific miRNAs, such as miR-206, during skeletal muscle differentiation.
  • These induced miRNAs contribute to the suppression of specific genes, like Fstl1 and Utrn.
  • This highlights a dual role for MyoD in activating muscle genes and repressing others via miRNAs.

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