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Schlafen-5 inhibits LINE-1 retrotransposition

Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strateg...

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Autores principales: Ding, Jiwei, Wang, Shujie, Liu, Qipeng, Duan, Yuqing, Cheng, Tingting, Ye, Zhongjie, Cui, Zhanding, Zhang, Ao, Liu, Qiuyu, Zhang, Zixiong, Zhang, Ning, Liu, Qian, An, Ni, Zhao, Jianyuan, Yi, Dongrong, Li, Quanjie, Wang, Jing, Zhang, Yongxin, Ma, Ling, Guo, Saisai, Wang, Jinhui, Liang, Chen, Zhou, Jinming, Cen, Shan, Li, Xiaoyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551903/
https://www.ncbi.nlm.nih.gov/pubmed/37810251
http://dx.doi.org/10.1016/j.isci.2023.107968
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author Ding, Jiwei
Wang, Shujie
Liu, Qipeng
Duan, Yuqing
Cheng, Tingting
Ye, Zhongjie
Cui, Zhanding
Zhang, Ao
Liu, Qiuyu
Zhang, Zixiong
Zhang, Ning
Liu, Qian
An, Ni
Zhao, Jianyuan
Yi, Dongrong
Li, Quanjie
Wang, Jing
Zhang, Yongxin
Ma, Ling
Guo, Saisai
Wang, Jinhui
Liang, Chen
Zhou, Jinming
Cen, Shan
Li, Xiaoyu
author_facet Ding, Jiwei
Wang, Shujie
Liu, Qipeng
Duan, Yuqing
Cheng, Tingting
Ye, Zhongjie
Cui, Zhanding
Zhang, Ao
Liu, Qiuyu
Zhang, Zixiong
Zhang, Ning
Liu, Qian
An, Ni
Zhao, Jianyuan
Yi, Dongrong
Li, Quanjie
Wang, Jing
Zhang, Yongxin
Ma, Ling
Guo, Saisai
Wang, Jinhui
Liang, Chen
Zhou, Jinming
Cen, Shan
Li, Xiaoyu
author_sort Ding, Jiwei
collection PubMed
description Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition. Mechanistic studies revealed that SLFN5 interrupts LINE-1 ribonucleoprotein particle (RNP) formation, thus diminishing nuclear entry of the LINE-1 RNA template and subsequent LINE-1 cDNA production. The ability of SLFN5 to bind to LINE-1 RNA and the involvement of the helicase domain of SLFN5 in its inhibitory activity suggest a mechanism that SLFN5 binds to LINE-1 RNA followed by dissociation of ORF1p through its helicase activity, resulting in impaired RNP formation. These data highlight a new mechanism of host cells to restrict LINE-1 mobilization.
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spelling pubmed-105519032023-10-06 Schlafen-5 inhibits LINE-1 retrotransposition Ding, Jiwei Wang, Shujie Liu, Qipeng Duan, Yuqing Cheng, Tingting Ye, Zhongjie Cui, Zhanding Zhang, Ao Liu, Qiuyu Zhang, Zixiong Zhang, Ning Liu, Qian An, Ni Zhao, Jianyuan Yi, Dongrong Li, Quanjie Wang, Jing Zhang, Yongxin Ma, Ling Guo, Saisai Wang, Jinhui Liang, Chen Zhou, Jinming Cen, Shan Li, Xiaoyu iScience Article Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition. Mechanistic studies revealed that SLFN5 interrupts LINE-1 ribonucleoprotein particle (RNP) formation, thus diminishing nuclear entry of the LINE-1 RNA template and subsequent LINE-1 cDNA production. The ability of SLFN5 to bind to LINE-1 RNA and the involvement of the helicase domain of SLFN5 in its inhibitory activity suggest a mechanism that SLFN5 binds to LINE-1 RNA followed by dissociation of ORF1p through its helicase activity, resulting in impaired RNP formation. These data highlight a new mechanism of host cells to restrict LINE-1 mobilization. Elsevier 2023-09-19 /pmc/articles/PMC10551903/ /pubmed/37810251 http://dx.doi.org/10.1016/j.isci.2023.107968 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
Ding, Jiwei
Wang, Shujie
Liu, Qipeng
Duan, Yuqing
Cheng, Tingting
Ye, Zhongjie
Cui, Zhanding
Zhang, Ao
Liu, Qiuyu
Zhang, Zixiong
Zhang, Ning
Liu, Qian
An, Ni
Zhao, Jianyuan
Yi, Dongrong
Li, Quanjie
Wang, Jing
Zhang, Yongxin
Ma, Ling
Guo, Saisai
Wang, Jinhui
Liang, Chen
Zhou, Jinming
Cen, Shan
Li, Xiaoyu
Schlafen-5 inhibits LINE-1 retrotransposition
title Schlafen-5 inhibits LINE-1 retrotransposition
title_full Schlafen-5 inhibits LINE-1 retrotransposition
title_fullStr Schlafen-5 inhibits LINE-1 retrotransposition
title_full_unstemmed Schlafen-5 inhibits LINE-1 retrotransposition
title_short Schlafen-5 inhibits LINE-1 retrotransposition
title_sort schlafen-5 inhibits line-1 retrotransposition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551903/
https://www.ncbi.nlm.nih.gov/pubmed/37810251
http://dx.doi.org/10.1016/j.isci.2023.107968
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