ArticleNature communications2022
RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 84 citations in OpenAlex.
- RNASEH2B loss and PARP inhibition in advanced prostate cancer.The Journal of clinical investigation · 2024Trial
- R-loops in colorectal cancer: mechanisms, mapping strategies, and therapeutic opportunities.Molecular biology reports · 2026Review
- When circular RNAs meet the genome: CiR-loops as chromatin regulators and disease drivers.Nucleic acids research · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity.Science advances · 2026Article
- Regulation of transcription by R loop-nucleated transcription condensate assembly.Cell & bioscience · 2026Review
- Non-B DNA structures and their contributions to genetic diversity, aging, and disease.Nucleic acids research · 2026Review
- The RNA exosome maintains cellular RNA homeostasis by controlling transcript abundance in the brain.Cell reports · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- Topoisomerase III-beta protects from immune dysregulation and tumorigenesis.Science advances · 2025Article
- Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.Journal of cell science · 2025Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- KDM5 demethylases suppress R-loop-mediated 'viral mimicry' and DNA damage in breast cancer cells.eLife · 2025Article
- From Genome to Geroscience: How DNA Damage Shapes Systemic Decline.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.Oncogene · 2025Article
- Ribonucleases in Mendelian disease: Characterization and insight from model organisms.Genes & diseases · 2025Review
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
RNase H2 is a specialized enzyme that degrades RNA in RNA/DNA hybrids and deficiency of this enzyme causes a severe neuroinflammatory disease, Aicardi Goutières syndrome (AGS). However, the molecular mechanism underlying AGS is still unclear. Here, we show that RNase H2 is associated with a subset of genes, in a transcription-dependent manner where it interacts with RNA Polymerase II. RNase H2 depletion impairs transcription leading to accumulation of R-loops, structures that comprise RNA/DNA hybrids and a displaced DNA strand, mainly associated with short and intronless genes. Importantly, accumulated R-loops are processed by XPG and XPF endonucleases which leads to DNA damage and activation of the immune response, features associated with AGS. Consequently, we uncover a key role for RNase H2 in the transcription of human genes by maintaining R-loop homeostasis. Our results provide insight into the mechanistic contribution of R-loops to AGS pathogenesis.
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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.