SLFN14 inhibits LINE-1 transposition activity
Received date: 2020-04-26
Revised date: 2020-05-22
Online published: 2020-05-25
Supported by
Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China No(2018ZX10301408-004);Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences No(CIFMS 2016-I2M-2-002)
Long interspersed nuclear element-1 (LINE-1) is the only active autonomous transposon in the human genome. Its transposition frequently induces host genome instability, leading to a variety of genetic diseases, including cancers. The host factors play important roles in inhibiting LINE-1 retrotransposition. As an important component of the immune system, the host factor SLFN14 has antiviral activity. Our laboratory shows that SLFN14 possesses potent inhibitory activity against LINE-1 retrotransposition. To explore the potential mechanism of SLFN14 inhibition, we analyzed its effects on transcription, translation, reverse transcription and insertion in the LINE-1 replication cycle. We confirmed that SLFN14 could suppress the LINE-1 mRNA level by affecting its transcription and degradation, thereby diminishing the protein and cDNA levels of LINE-1, which eventually block the LINE-1 retrotransposition. Further, by mapping the active domains of SLFN14, we found its inhibitory activity on LINE-1 being closely related to its endoribonuclease and ribosome binding domains. These results demonstrate the mechanism of SLFN14 in regulating LINE-1 replication, which further provide new insights for improving the regulation network of host factors for controlling genomic instability caused by LINE-1 replication.
Key words： transposition; retrotransposon; LINE-1; SLFN14; 5 ?-UTR internal promotor region;
Yang Mao, Jiwei Ding, Minshu Chen, Shan Cen, Xiaoyu Li . SLFN14 inhibits LINE-1 transposition activity[J]. Hereditas(Beijing), 2020 , 42(7) : 669 -679 . DOI: 10.16288/j.yczz.20-081
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