Advances in understanding telomerase assembly.
Advances in understanding telomerase assembly.
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DOI：
10.1042/bst20230269
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发表时间：
2023-12-20
影响因子：
3.9
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中科院分区：
文献类型：
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端粒酶是由端粒酶RNA（telomerase RNA，TR）构成的复杂的核糖核蛋白。端粒酶延长端粒对于维持干细胞和生殖细胞的增殖潜力是必不可少的，并且端粒酶在大多数癌症中被不适当地激活。在过去的二十年里，TR与其12种蛋白质辅因子的组装以及TR的5′端和3′端的成熟一直是研究的重点。人端粒酶的高分辨率Cryo-EM结构、TR 3′端的高通量测序以及各种端粒酶组分的活细胞成像极大地促进了我们对端粒酶生物发生的分子机制的理解，但许多重要问题仍未得到解决。在这篇综述中，我们将总结这些最新的进展，并强调剩余的关键问题，最终目标是靶向端粒酶组装，以抑制癌细胞中的端粒维持或促进端粒缩短疾病患者的端粒酶活性。
Telomerase is a complex ribonucleoprotein scaffolded by the telomerase RNA (TR). Telomere lengthening by telomerase is essential to maintain the proliferative potential of stem cells and germ cells, and telomerase is inappropriately activated in the majority of cancers. Assembly of TR with its 12 protein co-factors and the maturation of the 5′- and 3′-ends of TR have been the focus of intense research efforts over the past two decades. High-resolution Cryo-EM structures of human telomerase, high-throughput sequencing of the 3′ end of TR, and live cell imaging of various telomerase components have significantly advanced our understanding of the molecular mechanisms that govern telomerase biogenesis, yet many important questions remain unaddressed. In this review, we will summarize these recent advances and highlight the remaining key questions with the ultimate goal of targeting telomerase assembly to suppress telomere maintenance in cancer cells or to promote telomerase activity in patients affected by telomere shortening disorders.
影响因子：
14.9
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通讯作者：
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影响因子：
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作者：
Chen L;Chang HY;Artandi SE
通讯作者：
Artandi SE
影响因子：
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作者：
Ueda Y;Calado RT;Norberg A;Kajigaya S;Roos G;Hellstrom-Lindberg E;Young NS
通讯作者：
Young NS