Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo, Moscow, 143026, Russia.
Lomonosov Moscow State University, Department of Chemistry, Faculty of Bioengineering and Bioinformatics and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, 119992, Russia.
Sci Rep. 2019 Feb 8;9(1):1701. doi: 10.1038/s41598-018-38297-6.
Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. While telomerase is inactive in the majority of somatic cells, its activity determines the clonogenic potential of stem cells as a resource for tissue and organism regeneration. Reactivation of telomerase occurs during the process of immortalization in the majority of cancer cells. Telomerase is a ribonucleoprotein that contains telomerase reverse transcriptase and telomerase RNA components. The RNA processing mechanism of telomerase involves exosome trimming or degradation of the primary precursor. Recent data provide evidence that the competition between the processing and decay of telomerase RNA may regulate the amount of RNA at the physiological level. We show that termination of human telomerase RNA transcription is dependent on its promoter, which engages with the multisubunit complex Integrator to interact with RNA polymerase II and terminate transcription of the human telomerase RNA gene followed by further processing.
端粒是位于线性真核染色体末端的特殊 DNA-蛋白质结构。端粒长度决定了细胞的增殖潜力。端粒酶是端粒长度维持系统的关键组成部分。虽然端粒酶在大多数体细胞中不活跃，但它的活性决定了干细胞的克隆形成潜力，是组织和器官再生的资源。在大多数癌细胞的永生化过程中，端粒酶被重新激活。端粒酶是一种核糖核蛋白，包含端粒酶逆转录酶和端粒酶 RNA 成分。端粒酶的 RNA 加工机制涉及外切体修剪或初级前体的降解。最近的数据提供了证据，表明端粒酶 RNA 的加工和降解之间的竞争可能在生理水平上调节 RNA 的数量。我们表明，人类端粒酶 RNA 转录的终止依赖于其启动子，该启动子与多亚基复合物 Integrator 结合，与 RNA 聚合酶 II 相互作用，终止人类端粒酶 RNA 基因的转录，然后进一步加工。
