ArticleThe Journal of clinical investigation2015
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.Nature communications · 2026Pooled it
- Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus.Nature genetics · 2016Pooled it
- Topical Mupirocin Treatment Reduces Interferon and Myeloid Signatures in Cutaneous Lupus Erythematous Lesions Through Targeting of Staphylococcus Species.Arthritis & rheumatology (Hoboken, N.J.) · 2025Trial
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- A CRISPR/Cas9-induced blunt-end telomere system in S. pombe reveals RNase H2-dependent RNA primer removal at the terminal Okazaki fragment of lagging telomeres.Nucleic acids research · 2026Article
- PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.bioRxiv : the preprint server for biology · 2026Article
- No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases.European journal of immunology · 2026Article
- Viral mimicry acts as a tumor suppressor in colitis.Nature communications · 2026Article
- Review
- Genome-wide ribonucleotide detection in Archaea.Nucleic acids research · 2025Article
- Article
- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- Update on R-loops in genomic integrity: Formation, functions, and implications for human diseases.Genes & diseases · 2025Review
- Whole exome sequencing for identifying rare genetic variants related to idiopathic granulomatous mastitis.Clinical rheumatology · 2025Article
- Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.Current opinion in rheumatology · 2025Review
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.The Journal of experimental medicine · 2024Article
- De novo variants in immune regulatory genes in Down syndrome regression disorder.Journal of neurology · 2024Article
- Detection of ribonucleotides embedded in DNA by Nanopore sequencing.Communications biology · 2024Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
45 authors at 16 institutions in 4 countries.
Funding
Abstract
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity.
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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.