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DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0

Paraspeckles are mammal-specific membraneless nuclear bodies that participate in various biological processes. NONO, a central paraspeckle component, has been shown to play pivotal roles in DNA double-strand breaks (DSB) repair, whereas its underlying mechanism needs to be further disclosed. Here, u...

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Autores principales: Wang, Yun-Long, Zhao, Wan-Wen, Bai, Shao-Mei, Ma, Yan, Yin, Xin-Ke, Feng, Li-Li, Zeng, Guang-Dong, Wang, Fang, Feng, Wei-Xing, Zheng, Jian, Wang, Ying-Nai, Zeng, Bing, Liu, Quentin, Hung, Mien-Chie, Wan, Xiang-Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381602/
https://www.ncbi.nlm.nih.gov/pubmed/35974014
http://dx.doi.org/10.1038/s41419-022-05092-1
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author Wang, Yun-Long
Zhao, Wan-Wen
Bai, Shao-Mei
Ma, Yan
Yin, Xin-Ke
Feng, Li-Li
Zeng, Guang-Dong
Wang, Fang
Feng, Wei-Xing
Zheng, Jian
Wang, Ying-Nai
Zeng, Bing
Liu, Quentin
Hung, Mien-Chie
Wan, Xiang-Bo
author_facet Wang, Yun-Long
Zhao, Wan-Wen
Bai, Shao-Mei
Ma, Yan
Yin, Xin-Ke
Feng, Li-Li
Zeng, Guang-Dong
Wang, Fang
Feng, Wei-Xing
Zheng, Jian
Wang, Ying-Nai
Zeng, Bing
Liu, Quentin
Hung, Mien-Chie
Wan, Xiang-Bo
author_sort Wang, Yun-Long
collection PubMed
description Paraspeckles are mammal-specific membraneless nuclear bodies that participate in various biological processes. NONO, a central paraspeckle component, has been shown to play pivotal roles in DNA double-strand breaks (DSB) repair, whereas its underlying mechanism needs to be further disclosed. Here, using co-immunoprecipitation and mass spectrum, we identified ribosomal protein P0 (RPLP0) as a DSB-induced NONO-binding protein; RPLP0 binds to the RRM1 and RRM2 domains of NONO. Similar to NONO, RPLP0 enhances non-homologous end joining-mediated DSB repair, which was ascribed to a ribosome-independent manner. Interestingly, paraspeckles were induced as early as 15 min after irradiation; it further recruited nuclear RPLP0 to enhance its interaction with NONO. Radiation-induced NONO/RPLP0 complex subsequently anchored at the damaged DNA and increased the autophosphorylation of DNA-PK at Thr2609, thereby enhancing DSB repair. Consistently, in vivo and in vitro experiments showed that depletion of NONO sensitizes tumor cells to radiation. For patients with locally advanced rectal cancer, NONO expression was remarkably increased in tumor tissues and correlated with a poor response to radiochemotherapy. Our findings suggest a pivotal role of radiation-induced paraspeckles in DNA repair and tumor radioresistance, and provide a new insight into the ribosome-independent function of ribosomal proteins.
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spelling pubmed-93816022022-08-18 DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0 Wang, Yun-Long Zhao, Wan-Wen Bai, Shao-Mei Ma, Yan Yin, Xin-Ke Feng, Li-Li Zeng, Guang-Dong Wang, Fang Feng, Wei-Xing Zheng, Jian Wang, Ying-Nai Zeng, Bing Liu, Quentin Hung, Mien-Chie Wan, Xiang-Bo Cell Death Dis Article Paraspeckles are mammal-specific membraneless nuclear bodies that participate in various biological processes. NONO, a central paraspeckle component, has been shown to play pivotal roles in DNA double-strand breaks (DSB) repair, whereas its underlying mechanism needs to be further disclosed. Here, using co-immunoprecipitation and mass spectrum, we identified ribosomal protein P0 (RPLP0) as a DSB-induced NONO-binding protein; RPLP0 binds to the RRM1 and RRM2 domains of NONO. Similar to NONO, RPLP0 enhances non-homologous end joining-mediated DSB repair, which was ascribed to a ribosome-independent manner. Interestingly, paraspeckles were induced as early as 15 min after irradiation; it further recruited nuclear RPLP0 to enhance its interaction with NONO. Radiation-induced NONO/RPLP0 complex subsequently anchored at the damaged DNA and increased the autophosphorylation of DNA-PK at Thr2609, thereby enhancing DSB repair. Consistently, in vivo and in vitro experiments showed that depletion of NONO sensitizes tumor cells to radiation. For patients with locally advanced rectal cancer, NONO expression was remarkably increased in tumor tissues and correlated with a poor response to radiochemotherapy. Our findings suggest a pivotal role of radiation-induced paraspeckles in DNA repair and tumor radioresistance, and provide a new insight into the ribosome-independent function of ribosomal proteins. Nature Publishing Group UK 2022-08-16 /pmc/articles/PMC9381602/ /pubmed/35974014 http://dx.doi.org/10.1038/s41419-022-05092-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Yun-Long
Zhao, Wan-Wen
Bai, Shao-Mei
Ma, Yan
Yin, Xin-Ke
Feng, Li-Li
Zeng, Guang-Dong
Wang, Fang
Feng, Wei-Xing
Zheng, Jian
Wang, Ying-Nai
Zeng, Bing
Liu, Quentin
Hung, Mien-Chie
Wan, Xiang-Bo
DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title_full DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title_fullStr DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title_full_unstemmed DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title_short DNA damage-induced paraspeckle formation enhances DNA repair and tumor radioresistance by recruiting ribosomal protein P0
title_sort dna damage-induced paraspeckle formation enhances dna repair and tumor radioresistance by recruiting ribosomal protein p0
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381602/
https://www.ncbi.nlm.nih.gov/pubmed/35974014
http://dx.doi.org/10.1038/s41419-022-05092-1
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