Study on the mechanism of LNC004268 regulating sheep myoblast proliferation and differentiation through hnRNPK-CNOT2 Axis

The long non-coding RNAs (lncRNAs) can bind to transcription factors or RNA-binding proteins to play important regulatory roles in muscle growth and development. This study investigated the functional role of the LNC_004268 in sheep myoblast proliferation and differentiation, as well as its interaction with the RNA-binding protein hnRNPK and the downstream target gene CNOT2. LNC_004268 shows higher expression in the longissimus dorsi muscle of Small-tailed Han sheep (STH) compared to Sunite sheep (SNT) and is primarily localized in the nucleus. Functionally, LNC_004268 inhibits myoblast proliferation while promoting differentiation and myotube formation. Mechanistically, LNC_004268 binds hnRNPK, stabilizing CNOT2 mRNA. Actinomycin D (ACD) assays confirmed that LNC_004268 or hnRNPK overexpression delays CNOT2 mRNA decay, with combined expression further enhancing stability. Notably, CNOT2 functionally recapitulates LNC_004268's effects on myogenesis. Collectively, our study demonstrates that LNC_004268 regulates myoblast proliferation and differentiation by stabilizing CNOT2 mRNA via hnRNPK interaction, advancing understanding of lncRNA mediated muscle development regulation.