出芽酵母端粒酶全酶的低温电镜结构,这一成果由英国剑桥MRC分子生物学实验室
该课题组人员提出了芽殖酵母端粒酶的低温电镜结构,它表现出实质性的分歧,从其纤毛虫和脊椎动物的对应物。该结构揭示了端粒酶RNA TLC1形成的稳定核心;三个更短的端粒(Est)蛋白,Est1, Est2和Est3;Pop1/Pop6/Pop7复合物(Pop1/6/7)。TLC1, Est3和Pop1/6/7在复杂组装中起关键作用。该课题组在端粒酶逆转录酶(TERT)亚基Est2中发现了锌指(ZnF)基序,该基序对端粒酶功能至关重要。结构预测表明,在不同物种的TERT中存在ZnFs。这些发现提供了对酵母端粒酶的功能组织的见解,并强调了端粒酶全酶的进化多样性。
据了解,端粒酶是一种逆转录酶,在染色体末端合成端粒重复序列,保护基因组的完整性。
附:英文原文
Title: Cryo–electron microscopy structure of the budding yeast telomerase holoenzyme
Author: Hongmiao Hu, Hannah Neumann, Gabriela M. Teplitz, Elsa Franco-Echevarría, Pascal Chartrand, Raymund J. Wellinger, Thi Hoang Duong Nguyen
Issue&Volume: 2026-03-26
Abstract: Telomerase is a reverse transcriptase that synthesizes telomeric repeats at chromosome ends, safeguarding genome integrity. We present the cryo–electron microscopy structure of the budding yeast telomerase, which exhibits substantial divergence from its ciliate and vertebrate counterparts. The structure reveals a stable core formed by telomerase RNA TLC1; the three ever shorter telomere (Est) proteins, Est1, Est2 and Est3; and the Pop1/Pop6/Pop7 complex (Pop1/6/7). TLC1, Est3, and Pop1/6/7 serve critical roles in complex assembly. We identified a zinc finger (ZnF) motif in the telomerase reverse transcriptase (TERT) subunit Est2 that is crucial for telomerase function. Structure prediction suggests the presence of ZnFs in TERT from diverse species. These findings offer insights into the functional organization of yeast telomerase and underscore the evolutionary diversity of telomerase holoenzymes.
DOI: adz5344
Source: https://www.science.org/doi/10.1126/science.adz5344
