Year: 2018
Type: peer-review
Abstract: Telomerase is an RNA-protein complex (RNP) that extends telomeric DNA at the 3'-ends of chromosomes using its telomerase reverse transcriptase (TERT) and integral template-containing telomerase RNA (TER).Its activity is a critical determinant of human health, affecting aging, cancer, and stem cell renewal.Lack of atomic models of telomerase, particularly one with DNA bound, has limited our mechanistic understanding of telomeric DNA repeat synthesis.We report the 4.8Å resolution cryo-electron microscopy structure of active Tetrahymena telomerase bound to telomeric DNA.The catalytic core is an intricately interlocked structure of TERT and TER, including a previously structurally uncharacterized TERT domain that interacts with TEN domain to physically enclose TER and regulate activity.This complete structure of a telomerase catalytic core and its interactions with telomeric DNA from the template to telomere-interacting p50-TEB complex provides unanticipated insights into telomerase assembly and catalytic cycle and a new paradigm for a reverse transcriptase RNP.
Author: Jerry Shay
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, National Institutes of Health, National Institute of General Medical Sciences, Division of Materials Research, Division of Molecular and Cellular Biosciences, Division of Biological Infrastructure, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: G1326384438, G1395360581, G3138329133, G3299242641, MRI: Acquisition of a direct electron detector for the UCLA Titan electron microscope, Direct Detection Device for atomic resolution cryoEM of macromolecular complexes, West/Midwest Consortium for High-Resolution Cryo Electron Microscopy, G562934659, Structure and Function of Telomerase Proteins, Research Tranining in Cellular and Molecular Biology, Science and Technology Center on Real-Time Functional Imaging (STROBE), G9000031392, G9000087571, G9000100130, G9000265107
OpenAlex ID: W4255755584