Article
Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity. Public 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
- Dernière modification
- 2019-12-05
- Identifier
- PubMed ID: 27452471
- Resource Type
- Déclaration de droits
- DOI
- ISSN
- 2211-1247
- Language
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targetedMrnaDecayByRnaBindingProteinAuf1RegulatesAdultM.pdf | 2019-12-05 | Public | Télécharger |