Evolutionary perspectives of telomerase RNA structure and function.
TLDR
Telomerase provides unique insights into RNA and protein coevolution within RNP enzymes within telomerase enzymes.Abstract:
Telomerase is the eukaryotic solution to the 'end-replication problem' of linear chromosomes by synthesising the highly repetitive DNA constituent of telomeres, the nucleoprotein cap that protects chromosome termini. Functioning as a ribonucleoprotein (RNP) enzyme, telomerase is minimally composed of the highly conserved catalytic telomerase reverse transcriptase (TERT) and essential telomerase RNA (TR) component. Beyond merely providing the template for telomeric DNA synthesis, TR is an innate telomerase component and directly facilitates enzymatic function. TR accomplishes this by having evolved structural elements for stable assembly with the TERT protein and the regulation of the telomerase catalytic cycle. Despite its prominence and prevalence, TR has profoundly diverged in length, sequence, and biogenesis pathway among distinct evolutionary lineages. This diversity has generated numerous structural and mechanistic solutions for ensuring proper RNP formation and high fidelity telomeric DNA synthesis. Telomerase provides unique insights into RNA and protein coevolution within RNP enzymes.read more
Citations
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Journal ArticleDOI
Telomerase Mechanism of Telomere Synthesis
TL;DR: Studying of telomerase provides unique insights into cellular requirements for genome stability, tissue renewal, and tumorigenesis as well as new perspectives on dynamic ribonucleoprotein machines.
Journal ArticleDOI
Cryo-EM structure of substrate-bound human telomerase holoenzyme
Thi Hoang Duong Nguyen,Jane Tam,Robert A. Wu,Robert A. Wu,Basil J. Greber,Basil J. Greber,Daniel B. Toso,Eva Nogales,Kathleen Collins +8 more
TL;DR: The cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme is presented, showing two flexibly RNA-tethered lobes: the catalytic core with telomersase reverse transcriptase (TERT) and conserved motifs of telomerases RNA (hTR), and an H/ACA ribonucleoprotein (RNP).
Journal ArticleDOI
Structure of Telomerase with Telomeric DNA
TL;DR: 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 telomersase assembly and catalytic cycle and a new paradigm for a reverse transcriptase RNP.
Journal ArticleDOI
ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation
Dustin L. Gable,Valeriya Gaysinskaya,Christine C. Atik,C. Conover Talbot,Byunghak Kang,Susan E. Stanley,Elizabeth W. Pugh,Nuria Amat-Codina,Kara M. Schenk,Murat O. Arcasoy,Cory Brayton,Liliana Florea,Mary Armanios +12 more
TL;DR: The data identify a novel cause of human short telomere syndromes-familial pulmonary fibrosis and uncover nuclear exosome targeting as an essential 3' end maturation mechanism that vertebrate TR shares with replication-dependent histones.
Journal ArticleDOI
Structure of human telomerase holoenzyme with bound telomeric DNA
George E. Ghanim,Adam J. Fountain,Anne-Marie M. van Roon,Ramya Rangan,Rhiju Das,Kathleen Collins,Thi Hoang Duong Nguyen +6 more
TL;DR: In this paper, the structure of human telomerase holoenzyme bound to telomeric DNA was determined at sub-4 A resolution, which reveals crucial DNA-and RNA-binding interfaces in the active site of telomerases, as well as the locations of mutations that alter the activity of the enzyme.
References
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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