Human TRIM5? senses and restricts LINE-1 elements.

ABSTRACT: Mobile genetic elements have significantly shaped our genomic landscape. LINE-1 retroelements are the only autonomously active elements left in the human genome. Since new insertions can have detrimental consequences, cells need to efficiently control LINE-1 retrotransposition. Here, we demonstrate that the intrinsic immune factor TRIM5? senses and restricts LINE-1 retroelements. Previously, rhesus TRIM5? has been shown to efficiently block HIV-1 replication, while human TRIM5? was found to be less active. Surprisingly, we found that both human and rhesus TRIM5? efficiently repress human LINE-1 retrotransposition. TRIM5? interacts with LINE-1 ribonucleoprotein complexes in the cytoplasm, which is essential for restriction. In line with its postulated role as pattern recognition receptor, we show that TRIM5? also induces innate immune signaling upon interaction with LINE-1 ribonucleoprotein complexes. The signaling events activate the transcription factors AP-1 and NF-?B, leading to the down-regulation of LINE-1 promoter activity. Together, our findings identify LINE-1 as important target of human TRIM5?, which restricts and senses LINE-1 via two distinct mechanisms. Our results corroborate TRIM5? as pattern recognition receptor and shed light on its previously undescribed activity against mobile genetic elements, such as LINE-1, to protect the integrity of our genome.

SUBMITTER: Volkmann B 

PROVIDER: S-EPMC7395565 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature