A novel long non-coding RNA, Lnc-GAS7, modulates myosin heavy chain isoform switching via AMPK signaling in ovine muscle

The isoform composition of Myosin heavy chain (MyHC) in skeletal muscle is a major determinant of muscle function and meat quality in livestock. Long non-coding RNAs (lncRNAs) have been increasingly recognized as regulators of muscle development, yet their role in MyHC isoform switching in sheep remains unclear. In this study, we conducted lncRNA transcriptome profiling of three sheep skeletal muscles which have distinct MyHC isoform compositions: longissimus lumborum, psoas major, and soleus. A total of 288 differentially expressed lncRNAs potentially related to MyHC isoform regulation were identified. Among them, Lnc-GAS7 exhibited significant expression differences across muscle types and was selected for further functional validation. Knockdown of Lnc-GAS7 in ovine myoblasts promoted proliferation, suppressed differentiation, and increased expression of the slow-twitch MyHC I isoform. In contrast, overexpression inhibited proliferation, enhanced differentiation, and upregulated the fast-twitch MyHC IIb isoform. Mechanistically, gain- and loss-of-function studies show that both the knockdown and overexpression of Lnc-GAS7 significantly affected the expression of key genes in the AMP-activated protein kinase (AMPK) signaling pathway, while pharmacological manipulation of the AMPK pathway (Compound C inhibition and AICAR activation) attenuated these effects. These results identify Lnc-GAS7 as a novel modulator of MyHC isoform switching via AMPK signaling and offer novel insights into the regulatory mechanisms underlying muscle fiber plasticity in sheep.

Lnc-GAS7; Long non-coding RNA; Muscle fiber plasticity; Myosin heavy chain isoforms; Sheep skeletal muscle.