Article

 

Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity. Öffentlichkeit Deposited

https://scholar.colorado.edu/concern/articles/r494vk76p
Abstract
  • Following skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA-decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs containing 3' AU-rich elements (AREs). auf1(-/-) mice undergo accelerated skeletal muscle wasting with age and impaired skeletal muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1(-/-) satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs, including cell-autonomous overexpression of matrix metalloprotease MMP9. Secreted MMP9 degrades the skeletal muscle matrix, preventing satellite-cell-mediated regeneration and return to quiescence. Blocking MMP9 activity in auf1(-/-) mice restores skeletal muscle repair and maintenance of the satellite cell population. Control of ARE-mRNA decay by AUF1 represents a mechanism for adult stem cell regulation and is implicated in human skeletal muscle wasting diseases.
Creator
Date Issued
  • 2016-08-02
Academic Affiliation
Journal Title
Journal Issue/Number
  • 5
Journal Volume
  • 16
File Extent
  • 1379-1390
Subject
Zuletzt geändert
  • 2019-12-05
Identifier
  • PubMed ID: 27452471
Resource Type
Urheberrechts-Erklärung
DOI
ISSN
  • 2211-1247
Language

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