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

Devon M. Chenette; Adam B. Cadwallader; Tiffany L. Antwine; Lauren C. Larkin; Jinhua Wang; Bradley B. Olwin; Robert J. Schneider

doi:10.1016/j.celrep.2016.06.095

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

Devon M. Chenette, Adam B. Cadwallader, Tiffany L. Antwine, Lauren C. Larkin, Jinhua Wang, Bradley B. Olwin, Robert J. Schneider

Institute for Health Informatics

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1379-1390
Number of pages	12
Journal	Cell reports
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2016.06.095
State	Published - Aug 2 2016

Bibliographical note

Funding Information:
We thank Dr. Bruce Cronstein (NYU) for use of the DEXA. Technical assistance was provided by the NYU-CTSI Bioinformatics Core, Histopathology Core, Microscopy Core, Rodent Behavior Core, and Small Animal Imaging Core, supported in part by grant UL1 TR00038 from NCATS. This work was supported by NIH grants GM085693 and R24OD018339 to R.J.S., NIH T32 13-A0-S1-090476 to D.M.C., and AR049446 to B.B.O., who is also supported as a Senior Scholar in Aging Research by the Ellison Medical Foundation.

Publisher Copyright:
© 2016 The Authors

Keywords

AU-rich elements
AUF1
mRNA decay
muscle regeneration
muscle stem cells
satellite cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.celrep.2016.06.095

Find It

Find It at U of M Libraries

Cite this

@article{b81915a066b342dc9ac2314a639954ea,

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

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.",

keywords = "AU-rich elements, AUF1, mRNA decay, muscle regeneration, muscle stem cells, satellite cells",

author = "Chenette, {Devon M.} and Cadwallader, {Adam B.} and Antwine, {Tiffany L.} and Larkin, {Lauren C.} and Jinhua Wang and Olwin, {Bradley B.} and Schneider, {Robert J.}",

note = "Funding Information: We thank Dr. Bruce Cronstein (NYU) for use of the DEXA. Technical assistance was provided by the NYU-CTSI Bioinformatics Core, Histopathology Core, Microscopy Core, Rodent Behavior Core, and Small Animal Imaging Core, supported in part by grant UL1 TR00038 from NCATS. This work was supported by NIH grants GM085693 and R24OD018339 to R.J.S., NIH T32 13-A0-S1-090476 to D.M.C., and AR049446 to B.B.O., who is also supported as a Senior Scholar in Aging Research by the Ellison Medical Foundation. Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = aug,

day = "2",

doi = "10.1016/j.celrep.2016.06.095",

language = "English (US)",

volume = "16",

pages = "1379--1390",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Targeted mRNA Decay by RNA Binding Protein AUF1 Regulates Adult Muscle Stem Cell Fate, Promoting Skeletal Muscle Integrity

AU - Chenette, Devon M.

AU - Cadwallader, Adam B.

AU - Antwine, Tiffany L.

AU - Larkin, Lauren C.

AU - Wang, Jinhua

AU - Olwin, Bradley B.

AU - Schneider, Robert J.

N1 - Funding Information: We thank Dr. Bruce Cronstein (NYU) for use of the DEXA. Technical assistance was provided by the NYU-CTSI Bioinformatics Core, Histopathology Core, Microscopy Core, Rodent Behavior Core, and Small Animal Imaging Core, supported in part by grant UL1 TR00038 from NCATS. This work was supported by NIH grants GM085693 and R24OD018339 to R.J.S., NIH T32 13-A0-S1-090476 to D.M.C., and AR049446 to B.B.O., who is also supported as a Senior Scholar in Aging Research by the Ellison Medical Foundation. Publisher Copyright: © 2016 The Authors

PY - 2016/8/2

Y1 - 2016/8/2

N2 - 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.

AB - 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.

KW - AU-rich elements

KW - AUF1

KW - mRNA decay

KW - muscle regeneration

KW - muscle stem cells

KW - satellite cells

UR - http://www.scopus.com/inward/record.url?scp=84990052998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990052998&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.06.095

DO - 10.1016/j.celrep.2016.06.095

M3 - Article

C2 - 27452471

AN - SCOPUS:84990052998

SN - 2211-1247

VL - 16

SP - 1379

EP - 1390

JO - Cell reports

JF - Cell reports

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this