Title
Long noncoding RNA ZFP36L2-AS functions as a metabolic modulator to regulate muscle development.
Document Type
Article
Publication Date
4-21-2022
Publication Title
Cell Death Dis
Keywords
JGM, Humans, Muscle Development, Muscle, Skeletal, Muscular Atrophy, RNA, Long Noncoding, Transcription Factors
JAX Source
Cell Death Dis 2022 Apr 21; 13(4):389
Volume
13
Issue
4
First Page
389
Last Page
389
ISSN
2041-4889
PMID
35449125
DOI
https://doi.org/10.1038/s41419-022-04772-2
Abstract
Skeletal muscle is the largest metabolic organ in the body, and its metabolic flexibility is essential for maintaining systemic energy homeostasis. Metabolic inflexibility in muscles is a dominant cause of various metabolic disorders, impeding muscle development. In our previous study, we found lncRNA ZFP36L2-AS (for "ZFP36L2-antisense transcript") is specifically enriched in skeletal muscle. Here, we report that ZFP36L2-AS is upregulated during myogenic differentiation, and highly expressed in breast and leg muscle. In vitro, ZFP36L2-AS inhibits myoblast proliferation but promotes myoblast differentiation. In vivo, ZFP36L2-AS facilitates intramuscular fat deposition, as well as activates fast-twitch muscle phenotype and induces muscle atrophy. Mechanistically, ZFP36L2-AS interacts with acetyl-CoA carboxylase alpha (ACACA) and pyruvate carboxylase (PC) to induce ACACA dephosphorylation and damaged PC protein stability, thus modulating muscle metabolism. Meanwhile, ZFP36L2-AS can activate ACACA to reduce acetyl-CoA content, which enhances the inhibition of PC activity. Our findings present a novel model about the regulation of lncRNA on muscle metabolism.
Recommended Citation
Cai, Bolin; Ma, Manting; Zhang, Jing; Kong, Shaofen; Zhou, Zhen; Li, Zhenhui; Abdalla, Bahareldin Ali; Xu, Haiping; Zhang, Xiquan; Lawal, Raman Akinyanju; and Nie, Qinghua, "Long noncoding RNA ZFP36L2-AS functions as a metabolic modulator to regulate muscle development." (2022). Faculty Research 2022. 73.
https://mouseion.jax.org/stfb2022/73
Comments
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).