The MOV10 RNA helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice

作者：Yongjuan Guan, Hongyan Gao, N. Adrian Leu, Anastassios Vourekas, Panagiotis Alexiou, Manolis Maragkakis, Zhenlong Kang, Zissimos P. Mourelatos, Guanxiang Liang, P. Jeremy Wang · 发表于：PLoS Genetics · 年份：2023 · DOI：10.1371/journal.pgen.1010566 · 被引用次数：8 · 研究领域：Chromosomal and Genetic Variations、CRISPR and Genetic Engineering、Cytomegalovirus and herpesvirus research

Transposable elements constitute nearly half of the mammalian genome and play important roles in genome evolution. While a multitude of both transcriptional and post-transcriptional mechanisms exist to silence transposable elements, control of transposition in vivo remains poorly understood. MOV10, an RNA helicase, is an inhibitor of mobilization of retrotransposons and retroviruses in cell culture assays. Here we report that MOV10 restricts LINE1 retrotransposition in mice. Although MOV10 is broadly expressed, its loss causes only incomplete penetrance of embryonic lethality, and the surviving MOV10-deficient mice are healthy and fertile. Biochemically, MOV10 forms a complex with UPF1, a key component of the nonsense-mediated mRNA decay pathway, and primarily binds to the 3' UTR of somatically expressed transcripts in testis. Consequently, loss of MOV10 results in an altered transcriptome in testis. Analyses using a LINE1 reporter transgene reveal that loss of MOV10 leads to increased LINE1 retrotransposition in somatic and reproductive tissues from both embryos and adult mice. Moreover, the degree of LINE1 retrotransposition inhibition is dependent on the Mov10 gene dosage. Furthermore, MOV10 deficiency reduces reproductive fitness over successive generations. Our findings demonstrate that MOV10 attenuates LINE1 retrotransposition in a dosage-dependent manner in mice.