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

被引：37

作者：

Chenette, Devon M. ^{[1
]}

Cadwallader, Adam B. ^{[2
]}

Antwine, Tiffany L. ^{[2
]}

Larkin, Lauren C. ^{[1
]}

Wang, Jinhua ^{[3
]}

Olwin, Bradley B. ^{[2
]}

Schneider, Robert J. ^{[1
,4
]}

机构：

[1] NYU, Dept Microbiol, Sch Med, New York, NY 10016 USA

[2] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[3] NYU, Ctr Hlth Informat & Bioinformat, Sch Med, New York, NY 10016 USA

[4] NYU, Perlmutter Canc Ctr, Sch Med, New York, NY 10016 USA

来源：

CELL REPORTS | 2016年 / 16卷 / 05期

关键词：

SATELLITE CELLS; MUSCULAR-DYSTROPHY; SELF-RENEWAL; MOUSE MODEL; PROGENITOR CELLS; GENE-EXPRESSION; NUCLEAR IMPORT; REGENERATION; MYOGENESIS; MAINTENANCE;

D O I：

10.1016/j.celrep.2016.06.095

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 30 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.

引用

页码：1379 / 1390

页数：12

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