LncEDCH1 improves mitochondrial function to reduce muscle atrophy by interacting with SERCA2

Bolin Cai; Manting Ma; Jing Zhang; Zhijun Wang; Shaofen Kong; Zhen Zhou; Ling Lian; Jiannan Zhang; Juan Li; Yajun Wang; Hongmei Li; Xiquan Zhang; Qinghua Nie

doi:10.1016/j.omtn.2021.12.004

LncEDCH1 improves mitochondrial function to reduce muscle atrophy by interacting with SERCA2

Mol Ther Nucleic Acids. 2021 Dec 10:27:319-334. doi: 10.1016/j.omtn.2021.12.004. eCollection 2022 Mar 8.

Authors

Bolin Cai^{1

2}, Manting Ma^{1

2}, Jing Zhang^{1

2}, Zhijun Wang^{1

2}, Shaofen Kong^{1

2}, Zhen Zhou^{1

2}, Ling Lian³, Jiannan Zhang⁴, Juan Li⁴, Yajun Wang⁴, Hongmei Li^{1

2}, Xiquan Zhang^{1

2}, Qinghua Nie^{1

2}

Affiliations

¹ Lingnan Guangdong Laboratory of Modern Agriculture & State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, China.
² Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong 510642, China.
³ National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
⁴ Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.

Abstract

Skeletal muscle is a regulator of the body's energy expenditure and metabolism. Abnormal regulation of skeletal muscle-specific genes leads to various muscle diseases. Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in muscle growth and muscle atrophy. To explore the potential function of muscle-associated lncRNA, we analyzed our previous RNA-sequencing data and selected the lncRNA (LncEDCH1) as the research object. In this study, we report that LncEDCH1 is specifically enriched in skeletal muscle, and its transcriptional activity is positively regulated by transcription factor SP1. LncEDCH1 regulates myoblast proliferation and differentiation in vitro. In vivo, LncEDCH1 reduces intramuscular fat deposition, activates slow-twitch muscle phenotype, and inhibits muscle atrophy. Mechanistically, LncEDCH1 binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) protein to enhance SERCA2 protein stability and increase SERCA2 activity. Meanwhile, LncEDCH1 improves mitochondrial efficiency possibly through a SERCA2-mediated activation of the AMPK pathway. Our findings provide a strategy for using LncEDCH1 as an effective regulator for the treatment of muscle atrophy and energy metabolism.

Keywords: Ca2+ homeostasis; LncEDCH1; mitochondrial biogenesis; muscle atrophy; sarcoplasmic/ER calcium ATPase 2.