ArticleProceedings of the National Academy of Sciences of the United States of America2021
Introns encode dsRNAs undetected by RIG-I/MDA5/interferons and sensed via RNase L.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- Caspase-3 regulates RNA splicing and mitochondrial dynamics in microglia during Parkinson's disease.Cell death & disease · 2026Article
- TSniffer: unbiased de novo identification of RNA editing sites and quantification of editing activity in RNA-seq data.Genome biology · 2026Article
- Activated oligoadenylate synthetase-ribonuclease L pathway promotes endothelial pyroptosis and impairs diabetic wound healing via thioredoxin-interacting protein mMolecular biomedicine · 2025Article
- Comprehensive Mapping of Human dsRNAome Reveals Conservation, Neuronal Enrichment, and Intermolecular Interactions.bioRxiv : the preprint server for biology · 2025Article
- NMolecular medicine (Cambridge, Mass.) · 2024Review
- Inverted Alu repeats: friends or foes in the human transcriptome.Experimental & molecular medicine · 2024Review
- The competitive landscape of the dsRNA world.Molecular cell · 2024Review
- Activation of cytosolic RNA sensors by endogenous ligands: roles in disease pathogenesis.Frontiers in immunology · 2023Review
- The Unusual Role of Ribonuclease L in Innate Immunity.Wiley interdisciplinary reviews. RNAReview
- 2-5A-Mediated decay (2-5AMD): from antiviral defense to control of host RNA.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Double-stranded RNA (dsRNA), a hallmark viral material that activates antiviral interferon (IFN) responses, can appear in human cells also in the absence of viruses. We identify phosphorothioate DNAs (PS DNAs) as triggers of such endogenous dsRNA (endo-dsRNA). PS DNAs inhibit decay of nuclear RNAs and induce endo-dsRNA via accumulation of high levels of intronic and intergenic inverted retroelements (IIIR). IIIRs activate endo-dsRNA responses distinct from antiviral defense programs. IIIRs do not turn on transcriptional RIG-I/MDA5/IFN signaling, but they trigger the dsRNA-sensing pathways of OAS3/RNase L and PKR. Thus, nuclear RNA decay and nuclear-cytosolic RNA sorting actively protect from these innate immune responses to self. Our data suggest that the OAS3/RNase L and PKR arms of innate immunity diverge from antiviral IFN responses and monitor nuclear RNA decay by sensing cytosolic escape of IIIRs. OAS3 provides a receptor for IIIRs, whereas RNase L cleaves IIIR-carrying introns and intergenic RNAs.
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Registered trials
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