ArticleThe EMBO journal2016
Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 1 of them a synthesis that pooled it.
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Who cites it
152 citing papers in PubMed, 1 synthesis or guideline pooled it, 233 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3.Protein & cell · 2026Article
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- HeterozygousiScience · 2026Article
- Chronic and non-canonical cGAS-STING activation: implications for health, disease, cancer, and emerging therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- The PARP1-EXD2 axis orchestrates R-loop resolution to safeguard genome stability.Nature chemical biology · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- RNASEH2C enhances TRAF3IP1 to degrade RAI14 in lysosomes thus hindering macrophage antigen presentation and advancing liver cancer.Cell death & disease · 2025Article
- Article
- STING: a multifaced player in cellular homeostasis.Human molecular genetics · 2025Review
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Review
- Autocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers.Nature communications · 2025Article
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA.Scientific reports · 2025Article
- The Tumour Microenvironment and Epigenetic Regulation inCancers · 2024Review
- DNA-sensing pathways in health, autoinflammatory and autoimmune diseases.Nature immunology · 2024Review
- Synergistic action of human RNaseH2 and the RNA helicase-nuclease DDX3X in processing R-loops.Nucleic acids research · 2024Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Aicardi-Goutières syndrome (AGS) provides a monogenic model of nucleic acid-mediated inflammation relevant to the pathogenesis of systemic autoimmunity. Mutations that impair ribonuclease (RNase) H2 enzyme function are the most frequent cause of this autoinflammatory disorder of childhood and are also associated with systemic lupus erythematosus. Reduced processing of eitherRNA:DNAhybrid or genome-embedded ribonucleotide substrates is thought to lead to activation of a yet undefined nucleic acid-sensing pathway. Here, we establishRnaseh2b(A174T/A174T)knock-in mice as a subclinical model of disease, identifying significant interferon-stimulated gene (ISG) transcript upregulation that recapitulates theISGsignature seen inAGSpatients. The inflammatory response is dependent on the nucleic acid sensor cyclicGMP-AMPsynthase (cGAS) and its adaptorSTINGand is associated with reduced cellular ribonucleotide excision repair activity and increasedDNAdamage. This suggests thatcGAS/STINGis a key nucleic acid-sensing pathway relevant toAGS, providing additional insight into disease pathogenesis relevant to the development of therapeutics for this childhood-onset interferonopathy and adult systemic autoimmune disorders.
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Registered trials
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.