Authors:	Pérez-Martínez, Lara Öztürk, Merve Butter, Falk Luke, Brian
Title:	Npl3 stabilizes R-loops at telomeres to prevent accelerated replicative senescence
Online publication date:	6-Aug-2021
Year of first publication:	2020
Language:	english
Abstract:	Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R-loops become stabilized at critically short telomeres to promote their elongation through homology-directed repair (HDR), thereby counteracting senescence onset. Using a non-bias proteomic approach to detect telomere binding factors, we identified Npl3, an RNA-binding protein previously implicated in multiple RNA biogenesis processes. Using chromatin immunoprecipitation and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates with telomeres in an R-loop-dependent manner, as changes in R-loop levels, for example, at short telomeres, modulate the recruitment of Npl3 to chromosome ends. Through a series of genetic and biochemical approaches, we reveal that Npl3 binds to TERRA and stabilizes R-loops at short telomeres, which in turn promotes HDR and prevents premature replicative senescence onset. This may have implications for diseases associated with excessive telomere shortening.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-6239
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	EMBO reports 21 3
Pages or article number:	e49087
Publisher:	Wiley
Publisher place:	Hoboken, NJ u.a.
Issue date:	2020
ISSN:	1469-3178
Publisher URL:	https://doi.org/10.15252/embr.201949087
Publisher DOI:	10.15252/embr.201949087
Appears in collections:	JGU-Publikationen