Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40638752.
- Also identified by DOI 10.1126/science.adr5817 and PMC identifier 7618144.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Telomerase