The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

Zixiong Zhang; Ning Zhang; Saisai Guo; Qian Liu; Shujie Wang; Ao Zhang; Dongrong Yi; Jianyuan Zhao; Quanjie Li; Jing Wang; Yongxin Zhang; Ling Ma; Jiwei Ding; Shan Cen; Xiaoyu Li

doi:10.3389/fmicb.2022.891852

The Zinc-Finger protein ZCCHC3 inhibits LINE-1 retrotransposition

Front Microbiol. 2022 Oct 5:13:891852. doi: 10.3389/fmicb.2022.891852. eCollection 2022.

Authors

Zixiong Zhang¹, Ning Zhang¹, Saisai Guo¹, Qian Liu¹, Shujie Wang¹, Ao Zhang¹, Dongrong Yi¹, Jianyuan Zhao¹, Quanjie Li¹, Jing Wang¹, Yongxin Zhang¹, Ling Ma¹, Jiwei Ding¹, Shan Cen¹, Xiaoyu Li¹

Affiliation

¹ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical School, Beijing, China.

Abstract

Long-interspersed element 1 (LINE-1) is an autonomous non-LTR retrotransposon. Its replication can cause mutation and rearrangement of host genomic DNA, which may result in serious genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we reported that CCHC-type zinc-finger protein ZCCHC3 can repress LINE-1 retrotransposition, and this activity is closely related to its zinc-finger domain. Further studies show that ZCCHC3 can post-transcriptionally diminish the LINE-1 RNA level. The association of ZCCHC3 with both LINE-1 RNA and ORF1 suggests that ZCCHC3 interacts with LINE-1 RNP and consequently causes its RNA degradation. These data demonstrate collectively that ZCCHC3 contributes to the cellular control of LINE-1 replication.

Keywords: LINE-1; RNA; ZCCHC3; restricting factor; retrotransposon.