National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
2R35GM122579
米国
Howard Hughes Medical Institute (HHMI)
米国
Biotechnology and Biological Sciences Research Council (BBSRC)
BB/X01102X/1
英国
Chinese Scholarship Council
202206620047
中国
引用
ジャーナル: Science / 年: 2025 タイトル: Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization. 著者: 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 ...著者: 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 / 要旨: 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 ...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.
名称: Consensus dimer of human telomerase / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#11 詳細: A full human telomerase dimer, composed of two H/ACA RNP lobes and two catalytic cores