Telomerase is a ribonucleoprotein complex, the catalytic core of which includes the telomerase reverse transcriptase (TERT) and the non-coding human telomerase RNA (hTR), which serves as a template for the addition of telomeric repeats to chromosome ends. Telomerase expression is restricted in humans to certain cell types, and telomerase levels are tightly controlled in normal conditions. Increased levels of telomerase are found in the vast majority of human cancers, and we have recently begun to understand the mechanisms by which cancer cells increase telomerase activity. Conversely, germline mutations in telomerase-relevant genes that decrease telomerase function cause a range of genetic disorders, including dyskeratosis congenita, idiopathic pulmonary fibrosis and bone marrow failure. In this Review, we discuss the transcriptional regulation of human TERT, hTR processing, assembly of the telomerase complex, the cellular localization of telomerase and its recruitment to telomeres, and the regulation of telomerase activity. We also discuss the disease relevance of each of these steps of telomerase biogenesis.

端粒酶是一种核糖核蛋白复合物，其催化核心包括端粒酶逆转录酶 (TERT) 和非编码人类端粒酶 RNA (hTR)，后者可作为向染色体末端添加端粒重复序列的模板。端粒酶在人类中的表达仅限于某些细胞类型，并且端粒酶水平在正常条件下受到严格控制。在绝大多数人类癌症中发现端粒酶水平升高，我们最近开始了解癌细胞增加端粒酶活性的机制。相反，降低端粒酶功能的端粒酶相关基因的种系突变会导致一系列遗传疾病，包括先天性角化不良、特发性肺纤维化和骨髓衰竭。在这篇评论中，我们讨论了人类 TERT 的转录调控、hTR 加工、端粒酶复合物的组装、端粒酶的细胞定位及其向端粒的募集，以及端粒酶活性的调节。我们还讨论了端粒酶生物发生的每个步骤的疾病相关性。