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Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells

Embryonic stem cells (ESCs) are superior to differentiated cells to maintain genome stability, but the underlying mechanisms remain largely elusive. R-loops are constantly formed during transcription and are inducers of DNA damage if not resolved. Here we report that mouse ESCs (mESCs) can efficient...

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Autores principales: Gong, Daohua, Wang, Lin, Zhou, Hu, Gao, Jing, Zhang, Weidao, Zheng, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147553/
https://www.ncbi.nlm.nih.gov/pubmed/36931280
http://dx.doi.org/10.1016/j.stemcr.2023.02.003
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author Gong, Daohua
Wang, Lin
Zhou, Hu
Gao, Jing
Zhang, Weidao
Zheng, Ping
author_facet Gong, Daohua
Wang, Lin
Zhou, Hu
Gao, Jing
Zhang, Weidao
Zheng, Ping
author_sort Gong, Daohua
collection PubMed
description Embryonic stem cells (ESCs) are superior to differentiated cells to maintain genome stability, but the underlying mechanisms remain largely elusive. R-loops are constantly formed during transcription and are inducers of DNA damage if not resolved. Here we report that mouse ESCs (mESCs) can efficiently prevent unscheduled R-loop formation, and a long noncoding RNA Lnc530 plays regulatory role. Lnc530 is expressed in mESCs and localizes on R-loops. Depletion of Lnc530 in mESCs causes R-loop accumulation and DNA damage, whereas forced expression of Lnc530 in differentiated cells suppresses the R-loop formation. Mechanistically, Lnc530 associates with DDX5 and TDP-43 in an inter-dependent manner on R-loops. Formation of Lnc530-DDX5-TDP-43 complex substantially increases the local protein levels of DDX5 and TDP-43, both of which play critical roles in R-loop regulation. This study uncovers an efficient strategy to prevent R-loop accumulation and preserve genomic stability in mESCs and possibly other stem cell types.
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spelling pubmed-101475532023-04-29 Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells Gong, Daohua Wang, Lin Zhou, Hu Gao, Jing Zhang, Weidao Zheng, Ping Stem Cell Reports Article Embryonic stem cells (ESCs) are superior to differentiated cells to maintain genome stability, but the underlying mechanisms remain largely elusive. R-loops are constantly formed during transcription and are inducers of DNA damage if not resolved. Here we report that mouse ESCs (mESCs) can efficiently prevent unscheduled R-loop formation, and a long noncoding RNA Lnc530 plays regulatory role. Lnc530 is expressed in mESCs and localizes on R-loops. Depletion of Lnc530 in mESCs causes R-loop accumulation and DNA damage, whereas forced expression of Lnc530 in differentiated cells suppresses the R-loop formation. Mechanistically, Lnc530 associates with DDX5 and TDP-43 in an inter-dependent manner on R-loops. Formation of Lnc530-DDX5-TDP-43 complex substantially increases the local protein levels of DDX5 and TDP-43, both of which play critical roles in R-loop regulation. This study uncovers an efficient strategy to prevent R-loop accumulation and preserve genomic stability in mESCs and possibly other stem cell types. Elsevier 2023-03-16 /pmc/articles/PMC10147553/ /pubmed/36931280 http://dx.doi.org/10.1016/j.stemcr.2023.02.003 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Gong, Daohua
Wang, Lin
Zhou, Hu
Gao, Jing
Zhang, Weidao
Zheng, Ping
Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title_full Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title_fullStr Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title_full_unstemmed Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title_short Long noncoding RNA Lnc530 localizes on R-loops and regulates R-loop formation and genomic stability in mouse embryonic stem cells
title_sort long noncoding rna lnc530 localizes on r-loops and regulates r-loop formation and genomic stability in mouse embryonic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147553/
https://www.ncbi.nlm.nih.gov/pubmed/36931280
http://dx.doi.org/10.1016/j.stemcr.2023.02.003
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