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RBMX involves in telomere stability maintenance by regulating TERRA expression

Telomeric repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from subtelomeric to telomeric region of chromosome ends. TERRA is prone to form R-loop structures at telomeres by invading into telomeric DNA. Excessive telomere R-loops result in telomere insta...

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Autores principales: Liu, Jingfan, Zheng, Tian, Chen, Dandan, Huang, Junjiu, Zhao, Yong, Ma, Wenbin, Liu, Haiying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529574/
https://www.ncbi.nlm.nih.gov/pubmed/37756323
http://dx.doi.org/10.1371/journal.pgen.1010937
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author Liu, Jingfan
Zheng, Tian
Chen, Dandan
Huang, Junjiu
Zhao, Yong
Ma, Wenbin
Liu, Haiying
author_facet Liu, Jingfan
Zheng, Tian
Chen, Dandan
Huang, Junjiu
Zhao, Yong
Ma, Wenbin
Liu, Haiying
author_sort Liu, Jingfan
collection PubMed
description Telomeric repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from subtelomeric to telomeric region of chromosome ends. TERRA is prone to form R-loop structures at telomeres by invading into telomeric DNA. Excessive telomere R-loops result in telomere instability, so the TERRA level needs to be delicately modulated. However, the molecular mechanisms and factors controlling TERRA level are still largely unknown. In this study, we report that the RNA binding protein RBMX is a novel regulator of TERRA level and telomere integrity. The expression level of TERRA is significantly elevated in RBMX depleted cells, leading to enhanced telomere R-loop formation, replication stress, and telomere instability. We also found that RBMX binds to TERRA and the nuclear exosome targeting protein ZCCHC8 simultaneously, and that TERRA degradation slows down upon RBMX depletion, implying that RBMX promotes TERRA degradation by regulating its transportation to the nuclear exosome, which decays nuclear RNAs. Altogether, these findings uncover a new role of RBMX in TERRA expression regulation and telomere integrity maintenance, and raising RBMX as a potential target of cancer therapy.
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spelling pubmed-105295742023-09-28 RBMX involves in telomere stability maintenance by regulating TERRA expression Liu, Jingfan Zheng, Tian Chen, Dandan Huang, Junjiu Zhao, Yong Ma, Wenbin Liu, Haiying PLoS Genet Research Article Telomeric repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from subtelomeric to telomeric region of chromosome ends. TERRA is prone to form R-loop structures at telomeres by invading into telomeric DNA. Excessive telomere R-loops result in telomere instability, so the TERRA level needs to be delicately modulated. However, the molecular mechanisms and factors controlling TERRA level are still largely unknown. In this study, we report that the RNA binding protein RBMX is a novel regulator of TERRA level and telomere integrity. The expression level of TERRA is significantly elevated in RBMX depleted cells, leading to enhanced telomere R-loop formation, replication stress, and telomere instability. We also found that RBMX binds to TERRA and the nuclear exosome targeting protein ZCCHC8 simultaneously, and that TERRA degradation slows down upon RBMX depletion, implying that RBMX promotes TERRA degradation by regulating its transportation to the nuclear exosome, which decays nuclear RNAs. Altogether, these findings uncover a new role of RBMX in TERRA expression regulation and telomere integrity maintenance, and raising RBMX as a potential target of cancer therapy. Public Library of Science 2023-09-27 /pmc/articles/PMC10529574/ /pubmed/37756323 http://dx.doi.org/10.1371/journal.pgen.1010937 Text en © 2023 Liu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Liu, Jingfan
Zheng, Tian
Chen, Dandan
Huang, Junjiu
Zhao, Yong
Ma, Wenbin
Liu, Haiying
RBMX involves in telomere stability maintenance by regulating TERRA expression
title RBMX involves in telomere stability maintenance by regulating TERRA expression
title_full RBMX involves in telomere stability maintenance by regulating TERRA expression
title_fullStr RBMX involves in telomere stability maintenance by regulating TERRA expression
title_full_unstemmed RBMX involves in telomere stability maintenance by regulating TERRA expression
title_short RBMX involves in telomere stability maintenance by regulating TERRA expression
title_sort rbmx involves in telomere stability maintenance by regulating terra expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529574/
https://www.ncbi.nlm.nih.gov/pubmed/37756323
http://dx.doi.org/10.1371/journal.pgen.1010937
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