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.

Comments

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

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