Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, U.K.
Biochem Soc Trans. 2021 Nov 1;49(5):1927-1939. doi: 10.1042/BST20200042.
Telomerase ribonucleoprotein was discovered over three decades ago as a specialized reverse transcriptase that adds telomeric repeats to the ends of linear eukaryotic chromosomes. Telomerase plays key roles in maintaining genome stability; and its dysfunction and misregulation have been linked to different types of cancers and a spectrum of human genetic disorders. Over the years, a wealth of genetic and biochemical studies of human telomerase have illuminated its numerous fascinating features. Yet, structural studies of human telomerase have lagged behind due to various challenges. Recent technical developments in cryo-electron microscopy have allowed for the first detailed visualization of the human telomerase holoenzyme, revealing unprecedented insights into its active site and assembly. This review summarizes the cumulative work leading to the recent structural advances, as well as highlights how the future structural work will further advance our understanding of this enzyme.
端粒酶核糖核蛋白是三十多年前被发现的一种特殊的逆转录酶，它可以在线性真核染色体的末端添加端粒重复序列。端粒酶在维持基因组稳定性方面发挥着关键作用；其功能障碍和失调与不同类型的癌症和一系列人类遗传疾病有关。多年来，对人类端粒酶的大量遗传和生化研究阐明了其许多引人入胜的特征。然而，由于各种挑战，人类端粒酶的结构研究一直滞后。近年来，低温电子显微镜技术的发展使得首次能够详细观察到人类端粒酶全酶，从而对其活性位点和组装有了前所未有的了解。这篇综述总结了导致最近结构进展的累积工作，并强调了未来的结构工作将如何进一步增进我们对这种酶的理解。
