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 LNC₀04268 in sheep myoblast proliferation and differentiation, as well as its interaction with the RNA-binding protein hnRNPK and the downstream target gene CNOT2. LNC₀04268 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, LNC₀04268 inhibits myoblast proliferation while promoting differentiation and myotube formation. Mechanistically, LNC₀04268 binds hnRNPK, stabilizing CNOT2 mRNA. Actinomycin D (ACD) assays confirmed that LNC₀04268 or hnRNPK overexpression delays CNOT2 mRNA decay, with combined expression further enhancing stability. Notably, CNOT2 functionally recapitulates LNC₀04268's effects on myogenesis. Collectively, our study demonstrates that LNC₀04268 regulates myoblast proliferation and differentiation by stabilizing CNOT2 mRNA via hnRNPK interaction, advancing understanding of lncRNA mediated muscle development regulation.
Song et al. (Wed,) studied this question.