Long non-coding RNAs(lncRNAs)are important regulators of diverse biological processes,especially skeletal muscle cell differentiation.Most of the lncRNAs identified to date are localized in the nucleus and play regula...Long non-coding RNAs(lncRNAs)are important regulators of diverse biological processes,especially skeletal muscle cell differentiation.Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression.The cytoplasmic lncRNAs are less well understood.We previously identified a long intergenic non-coding RNA(linc-RNA)activator of myogenesis(Linc-RAM)that directly binds MyoD in the nucleus to enhance muscle cell differentiation.Here,we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells.To explore the molecular functions of cytoplasmic Linc-RAM,we sought to identify Linc-RAM-binding proteins.We report here that Linc-RAM physically interacts with glycogen phosphorylase(PYGM)in the cytoplasm.Knockdown of PYGM significantly attenuates the function of Linc-RAM in promoting muscle cell differentiation.Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner.Finally,we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells.Collectively,our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity.Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(91949106 and 31971080)the Natural Science Foundation of Beijing(7192125)+3 种基金the National Key R&D Program of China(2021YFA1100202)the Basic Research Projects of Basic Strengthening Program(2020-JCJQ-ZD-264)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-019)Postdoctoral Research Funding in Hebei province(B2021005012).
文摘Long non-coding RNAs(lncRNAs)are important regulators of diverse biological processes,especially skeletal muscle cell differentiation.Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression.The cytoplasmic lncRNAs are less well understood.We previously identified a long intergenic non-coding RNA(linc-RNA)activator of myogenesis(Linc-RAM)that directly binds MyoD in the nucleus to enhance muscle cell differentiation.Here,we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells.To explore the molecular functions of cytoplasmic Linc-RAM,we sought to identify Linc-RAM-binding proteins.We report here that Linc-RAM physically interacts with glycogen phosphorylase(PYGM)in the cytoplasm.Knockdown of PYGM significantly attenuates the function of Linc-RAM in promoting muscle cell differentiation.Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner.Finally,we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells.Collectively,our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity.Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.
