该课题组报告了人类端粒酶二聚体与端粒DNA结合的低温电镜（cryo-EM）结构。该结构揭示了端粒酶的Hinge和ACA盒（H/ACA） RNP介导的26亚基组装和二聚化界面。早衰疾病突变映射到这个界面。破坏二聚体的形成会影响细胞中RNP的组装、端粒酶活性和端粒的维持。他们的发现解决了围绕端粒酶二聚体的长期谜团，并提出了二聚体在端粒酶组装中的作用。
据了解，端粒酶核糖核蛋白（RNP）在染色体末端合成端粒重复序列，形成人类的端粒酶逆转录酶（TERT）和端粒酶RNA （hTR）。先前的结构研究表明，人类端粒酶通常是单体的，包含TERT和hTR的单一拷贝。存在二聚体配合物的证据，尽管其组成、高分辨率结构和功能仍不清楚。
附：英文原文
Title: Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization
Author: Sebastian Balch, Zala Sekne, Elsa Franco-Echevarría, Patryk Ludzia, Rachael C. Kretsch, Wenqing Sun, Haopeng Yu, George E. Ghanim, Sigurdur Thorkelsson, Yiliang Ding, Rhiju Das, Thi Hoang Duong Nguyen
Issue&Volume: 2025-07-10
Abstract: Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showed that human telomerase is typically monomeric, containing a single copy of TERT and hTR. Evidence for dimeric complexes exists, although the composition, high-resolution structure, and function remain elusive. Here, we report the cryo–electron microscopy (cryo-EM) structure of a human telomerase dimer bound to telomeric DNA. The structure reveals a 26-subunit assembly and a dimerization interface mediated by the Hinge and ACA box (H/ACA) RNP of telomerase. Premature aging disease mutations map to this interface. Disrupting dimer formation affects RNP assembly, bulk telomerase activity, and telomere maintenance in cells. Our findings address a long-standing enigma surrounding the telomerase dimer and suggest a role for the dimer in telomerase assembly.
DOI: adr5817
Source: https://www.science.org/doi/10.1126/science.adr5817