LncRNA RMST Functions as Enhancer of SUMOylation to Suppress GBM Cells Mitophagy

Background: Long non-coding RNAs (lncRNAs) play significant role in post-translational modifications of proteins, yet the importance of lncRNAs for sumoylation is unknown. Methods: RMST expression in glioma tissues and normal brain tissues was measured by RT-qPCR and in situ hybridization. The functional roles of RMST in astrocytomas were demonstrated by a series of in vitro experiments. The potential mechanisms of RMST for sumoylation was investigated by RNA immunoprecipitation,RNA pull-down, western blotting and co-immunoprecipitation assays. Findings: We first demonstrated the oncogenic activity of lncRNA RMST by inhibiting glioma cells mitophagy. We also first determined that RMST is an enhancer of FUS SUMOylation, especially boosting SUMO1 modification at K333. SUMOylation induced by RMST contributes to the interaction between FUS and hnRNPD and stabilized their expressionand cells mitophagy. Importantly, RMST as a highly expressed RNA in glioma is a better prognostic factor for glioma patients. Interpretation: our results demonstrated a previously unknown function of lncRNAs worked as an enhancer in FUS SUMOylation, and RMST will be a significant guide for the development of medications targeting gliomas. Funding: National Science Foundation of China;National Key Technology Research and Development program of the Ministry of Science and Technology of China;111 Project;Graduate Research and Innovation Projects of Central South University. Conflict of Interest: The authors declare no conflict of interest. Ethical Approval: All of the protocols were reviewed and approved by the Joint Ethics Committee of the Central South University Health Authority and performed in accordance with national guidelines. Animal experiments were approved by the Animal Care and Use Committee of Central South University.