Schlafen-5 inhibits LINE-1 retrotransposition

被引：0

作者：

Ding, Jiwei ^{[1
]}

Wang, Shujie ^{[1
]}

Liu, Qipeng ^{[1
]}

Duan, Yuqing ^{[1
]}

Cheng, Tingting ^{[1
]}

Ye, Zhongjie ^{[1
]}

Cui, Zhanding ^{[1
]}

Zhang, Ao ^{[1
]}

Liu, Qiuyu ^{[1
]}

Zhang, Zixiong ^{[1
]}

Zhang, Ning ^{[1
]}

Liu, Qian ^{[1
]}

An, Ni ^{[1
]}

Zhao, Jianyuan ^{[1
]}

Yi, Dongrong ^{[1
]}

Li, Quanjie ^{[1
]}

Wang, Jing ^{[1
]}

Zhang, Yongxin ^{[1
]}

Ma, Ling ^{[1
]}

Guo, Saisai ^{[1
]}

Wang, Jinhui ^{[2
]}

Liang, Chen ^{[3
]}

Zhou, Jinming ^{[4
]}

Cen, Shan ^{[1
]}

Li, Xiaoyu ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Beijing, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Beijing, Peoples R China

[3] Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada

[4] Zhejiang Normal Univ, Dept Chem, Key Lab, Minist Educ Adv Catalysis Mat, 688 Yingbin Rd, Jinhua 321004, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 10期

基金：

中国国家自然科学基金;

关键词：

L1; RETROTRANSPOSITION; REVERSE-TRANSCRIPTION; TRANSPOSABLE ELEMENTS; MALIGNANT-MELANOMA; GROWTH; RNA; IDENTIFICATION; EXPRESSION; FAMILY; MOV10;

D O I：

10.1016/j.isci.2023.107968

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in hu-mans, 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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页数：23

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