Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785115864322801664 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10551903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dingjiwei schlafen5inhibitsline1retrotransposition AT wangshujie schlafen5inhibitsline1retrotransposition AT liuqipeng schlafen5inhibitsline1retrotransposition AT duanyuqing schlafen5inhibitsline1retrotransposition AT chengtingting schlafen5inhibitsline1retrotransposition AT yezhongjie schlafen5inhibitsline1retrotransposition AT cuizhanding schlafen5inhibitsline1retrotransposition AT zhangao schlafen5inhibitsline1retrotransposition AT liuqiuyu schlafen5inhibitsline1retrotransposition AT zhangzixiong schlafen5inhibitsline1retrotransposition AT zhangning schlafen5inhibitsline1retrotransposition AT liuqian schlafen5inhibitsline1retrotransposition AT anni schlafen5inhibitsline1retrotransposition AT zhaojianyuan schlafen5inhibitsline1retrotransposition AT yidongrong schlafen5inhibitsline1retrotransposition AT liquanjie schlafen5inhibitsline1retrotransposition AT wangjing schlafen5inhibitsline1retrotransposition AT zhangyongxin schlafen5inhibitsline1retrotransposition AT maling schlafen5inhibitsline1retrotransposition AT guosaisai schlafen5inhibitsline1retrotransposition AT wangjinhui schlafen5inhibitsline1retrotransposition AT liangchen schlafen5inhibitsline1retrotransposition AT zhoujinming schlafen5inhibitsline1retrotransposition AT censhan schlafen5inhibitsline1retrotransposition AT lixiaoyu schlafen5inhibitsline1retrotransposition |