ArticleNature communications2023
Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 37 citations in OpenAlex.
- Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span.EMBO reports · 2026Article
- The Role of cGAS-STING-Driven PANoptosis in Neurodegenerative Diseases and Therapeutic Prospects.Cells · 2026Review
- cGAS-deficient mice display premature aging associated with derepression of LINE1 elements and inflammation.Nature aging · 2026Article
- SIRT1 Silences L1 Retrotransposons by Stabilizing Heterochromatin-Modifying Complexes.Aging cell · 2026Article
- LINE-1 Epigenetic Repression and Regulation of Immunity.Viruses · 2026Review
- A functional atlas of transposon-encoded products and their integration into host networks.Nature communications · 2026Article
- cGAS restricts PARP1-mediated microhomology-mediated end joining by suppressing poly-ADP-ribosylation.Cell death and differentiation · 2026Article
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Human cGAS Drives LINE-1 Transcriptional Activation to Trigger MAVS-Dependent Cellular Senescence.Aging cell · 2026Article
- The cGAS-STING pathway in cancer: friend or foe.Cell death & disease · 2026Review
- The Role of Non-LTR Retrotransposons in Sterile Inflammation: Mechanisms and Therapeutic Potential.Biomedicines · 2026Review
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Activation of cGAS-STING signaling in senescent cells promotes the aging process by remodeling the functions of the immune system.Biogerontology · 2025Review
- Pan-cancer analysis reveals context-dependent roles of LINE-1 ORF1p in immune regulation and copy number alterations.bioRxiv : the preprint server for biology · 2025Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- Transposable elements in health and disease: Molecular basis and clinical implications.Chinese medical journal · 2025Review
- Expression of LINE-1 elements is required for preimplantation development and totipotency.Genes & diseases · 2025Review
- The cGAS-STING pathway: a dual regulator of immune response in cancer and therapeutic implications.Journal of translational medicine · 2025Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclic GMP-AMP synthase (cGAS), initially identified as a cytosolic DNA sensor, detects DNA fragments to trigger an innate immune response. Recently, accumulating evidence reveals the presence of cGAS within the nucleus. However, the biological functions of nuclear cGAS are not fully understood. Here, we demonstrate that nuclear cGAS represses LINE-1 (L1) retrotransposition to preserve genome integrity in human cells. Mechanistically, the E3 ligase TRIM41 interacts with and ubiquitinates ORF2p to influence its stability, and cGAS enhances the association of ORF2p with TRIM41, thereby promoting TRIM41-mediated ORF2p degradation and the suppression of L1 retrotransposition. In response to DNA damage, cGAS is phosphorylated at serine residues 120 and 305 by CHK2, which promotes cGAS-TRIM41 association, facilitating TRIM41-mediated ORF2p degradation. Moreover, we show that nuclear cGAS mediates the repression of L1 retrotransposition in senescent cells induced by DNA damage agents. We also identify several cancer-associated cGAS mutations that abolish the suppressive effect on L1 retrotransposition by disrupting the CHK2-cGAS-TRIM41-ORF2p regulatory axis. Together, these findings indicate that nuclear cGAS exhibits an inhibitory function in L1 retrotransposition which could provide avenues for future interventions in both aging and tumorigenesis.
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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.