ArticleProceedings of the National Academy of Sciences of the United States of America2019
OAS-RNase L innate immune pathway mediates the cytotoxicity of a DNA-demethylating drug.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Benzothiazole derivatives target oligoadenylate synthetase and enhance RSV vaccine efficacy as adjuvants.Bioactive materials · 2027Article
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- The OAS-RNase L pathway: Insights from experiments of nature.Science immunology · 2026Review
- Identification and validation of pyroptosis patterns in AML via comprehensive bioinformatics analysis.Discover oncology · 2025Article
- ADAR1: from basic mechanisms to inhibitors.Trends in cell biology · 2025Review
- Targeting mitochondrial RNAs enhances the efficacy of the DNA-demethylating agents.Scientific reports · 2024Article
- Preferential cleavage of the coronavirus defective viral genome by cellular endoribonuclease with characteristics of RNase L.Virology journal · 2024Article
- Initiation of a ZAKα-dependent ribotoxic stress response by the innate immunity endoribonuclease RNase L.Cell reports · 2024Article
- SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion.Nature communications · 2024Article
- Article
- OAS3 Deubiquitination Due to E3 Ligase TRIM21 Downregulation Promotes Epithelial Cell Apoptosis and Drives Sepsis-induced Acute Lung Injury.International journal of biological sciences · 2024Article
- Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders.Molecular neurodegeneration · 2023Review
- The Many Faces of Oligoadenylate Synthetases.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
- RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma.Journal of molecular cell biology · 2023Article
- Article
- Stress granules are shock absorbers that prevent excessive innate immune responses to dsRNA.Molecular cell · 2023Article
- Activation of cytosolic RNA sensors by endogenous ligands: roles in disease pathogenesis.Frontiers in immunology · 2023Review
- PDE12 in type 1 diabetes.Scientific reports · 2022Article
- Values of OAS gene family in the expression signature, immune cell infiltration and prognosis of human bladder cancer.BMC cancer · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Drugs that reverse epigenetic silencing, such as the DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (AZA), have profound effects on transcription and tumor cell survival. AZA is an approved drug for myelodysplastic syndromes and acute myeloid leukemia, and is under investigation for different solid malignant tumors. AZA treatment generates self, double-stranded RNA (dsRNA), transcribed from hypomethylated repetitive elements. Self dsRNA accumulation in DNMTi-treated cells leads to type I IFN production and IFN-stimulated gene expression. Here we report that cell death in response to AZA treatment occurs through the 2',5'-oligoadenylate synthetase (OAS)-RNase L pathway. OASs are IFN-induced enzymes that synthesize the RNase L activator 2-5A in response to dsRNA. Cells deficient in RNase L or OAS1 to 3 are highly resistant to AZA, as are wild-type cells treated with a small-molecule inhibitor of RNase L. A small-molecule inhibitor of c-Jun NH
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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.