Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117437, Russia.
Chemistry Department and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Int J Mol Sci. 2023 Mar 6;24(5):5027. doi: 10.3390/ijms24055027.
Telomere length is associated with the proliferative potential of cells. Telomerase is an enzyme that elongates telomeres throughout the entire lifespan of an organism in stem cells, germ cells, and cells of constantly renewed tissues. It is activated during cellular division, including regeneration and immune responses. The biogenesis of telomerase components and their assembly and functional localization to the telomere is a complex system regulated at multiple levels, where each step must be tuned to the cellular requirements. Any defect in the function or localization of the components of the telomerase biogenesis and functional system will affect the maintenance of telomere length, which is critical to the processes of regeneration, immune response, embryonic development, and cancer progression. An understanding of the regulatory mechanisms of telomerase biogenesis and activity is necessary for the development of approaches toward manipulating telomerase to influence these processes. The present review focuses on the molecular mechanisms involved in the major steps of telomerase regulation and the role of post-transcriptional and post-translational modifications in telomerase biogenesis and function in yeast and vertebrates.
端粒长度与细胞的增殖潜能有关。端粒酶是一种在干细胞、生殖细胞和不断更新组织的细胞中，在整个生物体的寿命内延长端粒的酶。它在细胞分裂过程中被激活，包括再生和免疫反应。端粒酶成分的生物发生及其组装和功能定位到端粒是一个在多个水平上受到调节的复杂系统，其中每个步骤都必须根据细胞的需求进行调整。端粒酶生物发生和功能系统的组成部分的功能或定位的任何缺陷都会影响端粒长度的维持，这对再生、免疫反应、胚胎发育和癌症进展等过程至关重要。了解端粒酶生物发生和活性的调节机制对于开发操纵端粒酶以影响这些过程的方法是必要的。本综述重点介绍了参与端粒酶调节的主要步骤的分子机制，以及在酵母和脊椎动物中端粒酶生物发生和功能中翻译后和翻译后修饰的作用。
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