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- Title
Long noncoding RNA ZFP36L2-AS functions as a metabolic modulator to regulate muscle development.
- Authors
Cai, Bolin; Ma, Manting; Zhang, Jing; Kong, Shaofen; Zhou, Zhen; Li, Zhenhui; Abdalla, Bahareldin Ali; Xu, Haiping; Zhang, Xiquan; Lawal, Raman Akinyanju; Nie, Qinghua
- 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.
- Publication
Cell Death & Disease, 2022, Vol 13, Issue 4, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-022-04772-2