Project description:Recent studies indicate important roles for long noncoding RNAs (lncRNAs) as essential regulators of myogenesis and adult skeletal muscle regeneration. However, the specific roles of lncRNAs in myogenic differentiation of adult skeletal muscle stem cells and myogenesis are still largely unknown. Here we identify a lncRNA that is specifically enriched in skeletal muscle (myogenesis-associated lncRNA, in short, lnc-mg). In mice, conditional knockout of lnc-mg in skeletal muscle results in muscle atrophy and the loss of muscular endurance during exercise. Alternatively, skeletal muscle-specific overexpression of lnc-mg promotes muscle hypertrophy. In vitro analysis of primary skeletal muscle cells shows that lnc-mg increases gradually during myogenic differentiation and its overexpression improves cell differentiation. Mechanistically, lnc-mg promotes myogenesis, by functioning as a competing endogenous RNA (ceRNA) for microRNA-125b to control protein abundance of insulin-like growth factor 2. These findings identify lnc-mg as a novel noncoding regulator for muscle cell differentiation and skeletal muscle development.
Project description:Recent studies have indicated important roles for long noncoding RNAs (lncRNAs) as potential essential regulators of myogenesis and adult skeletal muscle regeneration. However, in vivo, the role and mechanism of lncRNAs in myogenic differentiation of adult skeletal muscle stem cells (MuSCs) and myogenesis are still largely unknown. Here, we identified a skeletal muscle specific-enriched lncRNA (myogenesis-associated lncRNA, short for lnc-mg). In vivo, skeletal muscle conditional knockout of lnc-mg resulted in muscle atrophy and the loss of muscular endurance during exercise. Alternatively, skeletal muscle-specific overexpression of lnc-mg promoted muscle hypertrophy in mice. In vitro analyses of primary skeletal muscle cells isolated from mice showed that expression of lnc-mg was increased gradually during myogenic differentiation and overexpressed lnc-mg improved cell differentiation. Mechanistically, lnc-mg promoted myogenesis, by functioning as a competing endogenous RNA (ceRNA) for miR-125b to control protein abundance of Igf2. These findings identify lnc-mg as a novel and important noncoding regulator for muscle cell differentiation and skeletal muscle development. In order to identify functional lncRNAs correlating with myogenesis, microarrays were performed to detect the lncRNAs expression profile in undifferentiated MuSCs (GM, growth media/GM) ) and differentiated MuSCs (DM, differentiation media/DM).
Project description:Recent studies have indicated important roles for long noncoding RNAs (lncRNAs) as potential essential regulators of myogenesis and adult skeletal muscle regeneration. However, in vivo, the role and mechanism of lncRNAs in myogenic differentiation of adult skeletal muscle stem cells (MuSCs) and myogenesis are still largely unknown. Here, we identified a skeletal muscle specific-enriched lncRNA (myogenesis-associated lncRNA, short for lnc-mg). In vivo, skeletal muscle conditional knockout of lnc-mg resulted in muscle atrophy and the loss of muscular endurance during exercise. Alternatively, skeletal muscle-specific overexpression of lnc-mg promoted muscle hypertrophy in mice. In vitro analyses of primary skeletal muscle cells isolated from mice showed that expression of lnc-mg was increased gradually during myogenic differentiation and overexpressed lnc-mg improved cell differentiation. Mechanistically, lnc-mg promoted myogenesis, by functioning as a competing endogenous RNA (ceRNA) for miR-125b to control protein abundance of Igf2. These findings identify lnc-mg as a novel and important noncoding regulator for muscle cell differentiation and skeletal muscle development. In order to test the hypothesis that lnc-mg may function as a ceRNA leading to the liberation of corresponding miRNA-targeted transcripts, microarrays were performed to detect miRNAs expression in lnc-mg overexpression and lnc-mg knockdown C2C12 cells.