ArticleNucleic acids research2017
Aicardi-Goutières syndrome protein TREX1 suppresses L1 and maintains genome integrity through exonuclease-independent ORF1p depletion.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Review
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Association of hyperactivated transposon expression with exacerbated immune activation in systemic lupus erythematosus.Mobile DNA · 2024Article
- DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair.Nucleic acids research · 2024Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- Micronucleus is not a potent inducer of the cGAS/STING pathway.Life science alliance · 2024Article
- Navigating the brain and aging: exploring the impact of transposable elements from health to disease.Frontiers in cell and developmental biology · 2024Review
- Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation.Nature communications · 2023Article
- Review
- STING antagonists, synthesizedRSC medicinal chemistry · 2023Article
- Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus.Mobile DNA · 2023Article
- Repetitive elements in aging and neurodegeneration.Trends in genetics : TIG · 2023Review
- PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.Nucleic acids research · 2023Article
- TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity.Clinical and experimental immunology · 2023Article
- The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction.Nature communications · 2023Article
- Article
- Generalized nuclear localization of retroelement transcripts.Mobile DNA · 2022Article
- TDP-43 safeguards the embryo genome from L1 retrotransposition.Science advances · 2022Article
- Nef Suppresses LINE-1 Retrotransposition through Two Distinct Mechanisms.Journal of virology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as systemic lupus erythematosus, Aicardi-Goutières syndrome (AGS) and familial chilblain lupus. However, TREX1 mutants competent for DNA exonuclease activity are also linked to AGS. Here, we report a nuclease-independent involvement of TREX1 in preventing the L1 retrotransposon-induced DNA damage response. TREX1 interacted with ORF1p and altered its intracellular localization. Furthermore, TREX1 triggered ORF1p depletion and reduced the L1-mediated nicking of genomic DNA. TREX1 mutants related to AGS were deficient in inducing ORF1p depletion and could not prevent L1-mediated DNA damage. Therefore, our findings not only reveal a new mechanism for TREX1-mediated L1 suppression and uncover a new function for TREX1 in protein destabilization, but they also suggest a novel mechanism for TREX1-mediated suppression of innate immune activation through maintaining genome integrity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.