RNA, volume 26, issue 12, pages 1787-1800

Folding heterogeneity in the essential human telomerase RNA three-way junction

Palka Christina 1
Forino Nicholas M 2
Hentschel Jendrik 1
Khatri Purvesh 3
Stone Michael D. 1
1
 
Department of Chemistry and Biochemistry, UniVersity of California, Santa Cruz, California 95064, USA.
2
 
Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA
3
 
Department of Physics, Stanford University, Stanford, California 94305, USA.
Publication typeJournal Article
Publication date2020-08-19
Journal: RNA
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor4.5
ISSN13558382, 14699001
Molecular Biology
Abstract

Telomeres safeguard the genome by suppressing illicit DNA damage responses at chromosome termini. To compensate for incomplete DNA replication at telomeres, most continually dividing cells, including many cancers, express the telomerase ribonucleoprotein (RNP) complex. Telomerase maintains telomere length by catalyzing de novo synthesis of short DNA repeats using an internal telomerase RNA (TR) template. TRs from diverse species harbor structurally conserved domains that contribute to RNP biogenesis and function. In vertebrate TRs, the conserved regions 4 and 5 (CR4/5) fold into a three-way junction (TWJ) that binds directly to the telomerase catalytic protein subunit and is required for telomerase function. We have analyzed the structural properties of the human TR (hTR) CR4/5 domain using a combination of in vitro chemical mapping, secondary structural modeling, and single-molecule structural analysis. Our data suggest the essential P6.1 stem–loop within CR4/5 is not stably folded in the absence of the telomerase reverse transcriptase in vitro. Rather, the hTR CR4/5 domain adopts a heterogeneous ensemble of conformations. Finally, single-molecule FRET measurements of CR4/5 and a mutant designed to stabilize the P6.1 stem demonstrate that TERT binding selects for a structural conformation of CR4/5 that is not the dominant state of the TERT-free in vitro RNA ensemble.

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Palka C. et al. Folding heterogeneity in the essential human telomerase RNA three-way junction // RNA. 2020. Vol. 26. No. 12. pp. 1787-1800.
GOST all authors (up to 50) Copy
Palka C., Forino N. M., Hentschel J., Khatri P., Stone M. D. Folding heterogeneity in the essential human telomerase RNA three-way junction // RNA. 2020. Vol. 26. No. 12. pp. 1787-1800.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1261/rna.077255.120
UR - https://doi.org/10.1261%2Frna.077255.120
TI - Folding heterogeneity in the essential human telomerase RNA three-way junction
T2 - RNA
AU - Palka, Christina
AU - Forino, Nicholas M
AU - Hentschel, Jendrik
AU - Khatri, Purvesh
AU - Stone, Michael D.
PY - 2020
DA - 2020/08/19 00:00:00
PB - Cold Spring Harbor Laboratory
SP - 1787-1800
IS - 12
VL - 26
PMID - 32817241
SN - 1355-8382
SN - 1469-9001
ER -
BibTex |
Cite this
BibTex Copy
@article{2020_Palka,
author = {Christina Palka and Nicholas M Forino and Jendrik Hentschel and Purvesh Khatri and Michael D. Stone},
title = {Folding heterogeneity in the essential human telomerase RNA three-way junction},
journal = {RNA},
year = {2020},
volume = {26},
publisher = {Cold Spring Harbor Laboratory},
month = {aug},
url = {https://doi.org/10.1261%2Frna.077255.120},
number = {12},
pages = {1787--1800},
doi = {10.1261/rna.077255.120}
}
MLA
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MLA Copy
Palka, Christina, et al. “Folding heterogeneity in the essential human telomerase RNA three-way junction.” RNA, vol. 26, no. 12, Aug. 2020, pp. 1787-1800. https://doi.org/10.1261%2Frna.077255.120.
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