The m6A methyltransferase METTL3 regulates muscle maintenance and growth in mice

Jennifer M. Petrosino, Scott A. Hinger, Volha A. Golubeva, Juan M. Barajas, Lisa E. Dorn, Chitra C. Iyer, Hui-Lung Sun, W. David Arnold, Chuan He and Federica Accornero ()
Additional contact information
Jennifer M. Petrosino: The Ohio State University
Scott A. Hinger: The Ohio State University
Volha A. Golubeva: The Ohio State University
Juan M. Barajas: The Ohio State University
Lisa E. Dorn: The Ohio State University
Chitra C. Iyer: The Ohio State University
Hui-Lung Sun: The University of Chicago
W. David Arnold: The Ohio State University
Chuan He: The University of Chicago
Federica Accornero: The Ohio State University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (m6A) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the m6A enzyme), and concomitantly m6A, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27848-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27848-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27848-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().