Liu Changhong, Peng Zixuan, Li Peiyao, Fu Haijuan, Feng Jianbo, Zhang Yan, Liu Tao, Liu Yang, Liu Qing, Liu Qiang, Li Di, Wu Minghua
Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China; Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, Shandong 250033, China.
Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1198-1208. doi: 10.1016/j.omtn.2020.01.008. Epub 2020 Jan 18.
Long non-coding RNAs (lncRNAs) play a significant role in post-translational modifications of proteins, yet the importance of lncRNAs for SUMOylation is unknown. rhabdomyosarcoma 2 associated transcript (RMST) expression in glioma tissues and normal brain tissues was measured by quantitative real-time PCR 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 were investigated by RNA immunoprecipitation, RNA pull-down, western blotting, and coimmunoprecipitation assays. 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 heterogeneous nuclear ribonucleoprotein D (hnRNPD) and stabilized their expression and cells mitophagy. Importantly, lncRNA RMST could serve as a promising prognostic factor for glioma patients. 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.
长链非编码RNA（lncRNAs）在蛋白质的翻译后修饰中发挥着重要作用，然而lncRNAs对SUMO化的重要性尚不清楚。通过定量实时PCR和原位杂交检测了横纹肌肉瘤2相关转录本（RMST）在胶质瘤组织和正常脑组织中的表达。通过一系列体外实验证明了RMST在星形细胞瘤中的功能作用。通过RNA免疫沉淀、RNA下拉、蛋白质免疫印迹和免疫共沉淀实验研究了RMST促进SUMO化的潜在机制。我们首先通过抑制胶质瘤细胞的线粒体自噬证明了lncRNA RMST的致癌活性。我们还首次确定RMST是FUS SUMO化的增强子，特别是增强了K333位点的SUMO1修饰。RMST诱导的SUMO化促进了FUS与不均一核核糖核蛋白D（hnRNPD）之间的相互作用，并稳定了它们的表达以及细胞的线粒体自噬。重要的是，lncRNA RMST可作为胶质瘤患者一个有前景的预后因素。我们的结果证明了lncRNAs作为FUS SUMO化增强子的一个前所未知的功能，并且RMST将为针对胶质瘤的药物开发提供重要指导。
