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Human TRIM5α senses and restricts LINE-1 elements
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2020
-
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 TRIM5α senses and restricts LINE-1 retroelements. Previously, rhesus TRIM5α has been shown to efficiently block HIV-1 replication, while human TRIM5α was found to be less active. Surprisingly, we found that both human and rhesus TRIM5α efficiently repress human LINE-1 retrotransposition. TRIM5α 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 TRIM5α also induces innate immune signaling upon interaction with LINE-1 ribonucleoprotein complexes. The signaling events activate the transcription factors AP-1 and NF-κB, leading to the down-regulation of LINE-1 promoter activity. Together, our findings identify LINE-1 as important target of human TRIM5α, which restricts and senses LINE-1 via two distinct mechanisms. Our results corroborate TRIM5α 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.
- Subjects :
- Ubiquitin-Protein Ligases
Gene Expression
Retrotransposon
Biology
Genome
Antiviral Restriction Factors
Tripartite Motif Proteins
Genes, Reporter
Animals
Humans
Protein Interaction Domains and Motifs
Promoter Regions, Genetic
Transcription factor
Ribonucleoprotein
Multidisciplinary
Innate immune system
Pattern recognition receptor
Biological Sciences
Macaca mulatta
Immunity, Innate
Cell biology
Protein Transport
Long Interspersed Nucleotide Elements
Host-Pathogen Interactions
Human genome
Mobile genetic elements
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 117
- Issue :
- 30
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....0558f9af500d1d1a783685f785e210b3