Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity

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.

Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice

General anesthesia severely affects the metabolites in the brain.Glycogen,principally stored in astrocytes and providing the short-term delivery of substrates to neurons,has been implicated as an affected molecule.However,whether glycogen plays a pivotal role in modulating anesthesia-arousal remains unclear.Here,we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions.Glycogen synthase(GS)and glycogen phosphorylase(GP),key enzymes of glycogen metabolism,showed increased activity after isoflurane exposure.Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-Darabinitol(DAB),a GP antagonist,we found a prolonged time of emergence from anesthesia and an enhancedδfrequency in the EEG(electroencephalogram).In addition,augmented expression of glycogenolysis genes in glycogen phosphorylase,brain(Pygb)knock-in(PygbH11/H11)mice resulted in delayed induction of anesthesia,a shortened emergence time,and a lower ratio of EEG-δ.Our findings revealed a role of brain glycogen in regulating anesthesiaarousal,providing a potential target for modulating anesthesia.