1. Developmental Biology
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Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay

  1. Melissa A Hausburg
  2. Jason D Doles
  3. Sandra L Clement
  4. Adam B Cadwallader
  5. Monica N Hall
  6. Perry J Blackshear
  7. Jens Lykke-Andersen
  8. Bradley B Olwin  Is a corresponding author
  1. Ampio Pharmaceuticals, Inc., United States
  2. University of Colorado, United States
  3. University of Colorado Boulder, United States
Research Article
  • Cited 59
  • Views 2,639
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Cite this article as: eLife 2015;4:e03390 doi: 10.7554/eLife.03390

Abstract

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis.

Article and author information

Author details

  1. Melissa A Hausburg

    Ampio Pharmaceuticals, Inc., Englewood, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jason D Doles

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sandra L Clement

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Adam B Cadwallader

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Monica N Hall

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Perry J Blackshear

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jens Lykke-Andersen

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Bradley B Olwin

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, United States
    For correspondence
    olwin@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#1012.01, #1104.08) of the University of Colorado-Boulder.

Reviewing Editor

  1. Margaret Buckingham, Institut Pasteur, France

Publication history

  1. Received: May 16, 2014
  2. Accepted: March 26, 2015
  3. Accepted Manuscript published: March 27, 2015 (version 1)
  4. Version of Record published: April 30, 2015 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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