Shliapina Viktoriia, Koriagina Mariia, Vasilkova Daria, Govorun Vadim, Dontsova Olga, Rubtsova Maria
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Department of Chemistry and A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Front Cell Dev Biol. 2021 Dec 7;9:754611. doi: 10.3389/fcell.2021.754611. eCollection 2021.
Cell proliferation is associated with increased energy and nutrients consumption. Metabolism switch from oxidative phosphorylation to glycolysis and telomerase activity are induced during stimulation of proliferation, such as tumorigenesis, immune cell activation, and stem cell differentiation, among others. Telomerase RNA is one of the core components of the telomerase complex and participates in survival mechanisms that are activated under stress conditions. Human telomerase RNA protein (hTERP) is encoded by telomerase RNA and has been recently shown to be involved in autophagy regulation. In this study, we demonstrated the role of hTERP in the modulation of signaling pathways regulating autophagy, protein biosynthesis, and cell proliferation. The AMPK signaling pathway was affected in cells deficient of hTERP and when hTERP was overexpressed. The appearance of hTERP is important for metabolism switching associated with the accelerated proliferation of cells in healthy and pathological processes. These findings demonstrate the connection between telomerase RNA biogenesis and function and signaling pathways.
细胞增殖与能量和营养物质消耗增加有关。在增殖刺激过程中，如肿瘤发生、免疫细胞激活和干细胞分化等，会诱导代谢从氧化磷酸化转变为糖酵解，并激活端粒酶活性。端粒酶RNA是端粒酶复合物的核心成分之一，参与在应激条件下被激活的生存机制。人端粒酶RNA蛋白（hTERP）由端粒酶RNA编码，最近已证明其参与自噬调节。在本研究中，我们证明了hTERP在调节自噬、蛋白质生物合成和细胞增殖的信号通路中的作用。在缺乏hTERP的细胞以及hTERP过表达时，AMPK信号通路均受到影响。hTERP的出现对于健康和病理过程中与细胞加速增殖相关的代谢转换很重要。这些发现证明了端粒酶RNA生物合成与功能以及信号通路之间的联系。
