TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity

Abstract Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal e...

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Autores principales:	Yang Mei, Zhong Deng, Olga Vladimirova, Nitish Gulve, F. Brad Johnson, William C. Drosopoulos, Carl L. Schildkraut, Paul M. Lieberman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/66afc9aff8e74ec3a03afa244b0f1666
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spelling	oai:doaj.org-article:66afc9aff8e74ec3a03afa244b0f16662021-12-02T12:09:06ZTERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity10.1038/s41598-021-82406-x2045-2322https://doaj.org/article/66afc9aff8e74ec3a03afa244b0f16662021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82406-xhttps://doaj.org/toc/2045-2322Abstract Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal end protection. The basic N-terminal Gly/Arg-rich (GAR) domain of telomeric repeat-binding factor 2 (TRF2) can bind TERRA but the structural basis and significance of this interaction remains poorly understood. Here, we show that TRF2 GAR recognizes G-quadruplex features of TERRA. We show that small molecules that disrupt the TERRA-TRF2 GAR complex, such as N-methyl mesoporphyrin IX (NMM) or genetic deletion of TRF2 GAR domain, result in the loss of TERRA, and the induction of γH2AX-associated telomeric DNA damage associated with decreased telomere length, and increased telomere aberrations, including telomere fragility. Taken together, our data indicates that the G-quadruplex structure of TERRA is an important recognition element for TRF2 GAR domain and this interaction between TRF2 GAR and TERRA is essential to maintain telomere stability.Yang MeiZhong DengOlga VladimirovaNitish GulveF. Brad JohnsonWilliam C. DrosopoulosCarl L. SchildkrautPaul M. LiebermanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yang Mei Zhong Deng Olga Vladimirova Nitish Gulve F. Brad Johnson William C. Drosopoulos Carl L. Schildkraut Paul M. Lieberman TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
description	Abstract Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal end protection. The basic N-terminal Gly/Arg-rich (GAR) domain of telomeric repeat-binding factor 2 (TRF2) can bind TERRA but the structural basis and significance of this interaction remains poorly understood. Here, we show that TRF2 GAR recognizes G-quadruplex features of TERRA. We show that small molecules that disrupt the TERRA-TRF2 GAR complex, such as N-methyl mesoporphyrin IX (NMM) or genetic deletion of TRF2 GAR domain, result in the loss of TERRA, and the induction of γH2AX-associated telomeric DNA damage associated with decreased telomere length, and increased telomere aberrations, including telomere fragility. Taken together, our data indicates that the G-quadruplex structure of TERRA is an important recognition element for TRF2 GAR domain and this interaction between TRF2 GAR and TERRA is essential to maintain telomere stability.
format	article
author	Yang Mei Zhong Deng Olga Vladimirova Nitish Gulve F. Brad Johnson William C. Drosopoulos Carl L. Schildkraut Paul M. Lieberman
author_facet	Yang Mei Zhong Deng Olga Vladimirova Nitish Gulve F. Brad Johnson William C. Drosopoulos Carl L. Schildkraut Paul M. Lieberman
author_sort	Yang Mei
title	TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
title_short	TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
title_full	TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
title_fullStr	TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
title_full_unstemmed	TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity
title_sort	terra g-quadruplex rna interaction with trf2 gar domain is required for telomere integrity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/66afc9aff8e74ec3a03afa244b0f1666
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TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity

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