ArticleImmunity2021
Protein kinase R and the integrated stress response drive immunopathology caused by mutations in the RNA deaminase ADAR1.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 119 citations in OpenAlex.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- ZBP1 specifically binds pre-formed Z-RNA, limiting its potential pool of nucleic acid ligands compared to ADAR1.Nucleic acids research · 2026Article
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- MDA5 and the integrated stress response control sex-specific type 1 diabetes onset in NOD mice.bioRxiv : the preprint server for biology · 2026Article
- Neuron-specific deletion of ADAR1 induces brain malformation and early postnatal lethality.Journal of neuroinflammation · 2026Article
- Molecular Regulation of HIV-1 Expression and Persistence Across Diverse Cellular Reservoirs.International journal of molecular sciences · 2026Review
- Adenosine-to-Inosine (A-to-I) RNA Editing by ADAR1 to Control RNA Sensing in Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.Cell reports · 2026Article
- Two codes of RNA editing by deamination in human diseases.Experimental & molecular medicine · 2026Review
- HeterozygousiScience · 2026Article
- The OAS-RNase L pathway: Insights from experiments of nature.Science immunology · 2026Review
- RNA-triggered innate immunity: friend and foe.Frontiers in genetics · 2026Review
- Integrated stress response inhibition prolongs the lifespan of a Pelizaeus-Merzbacher disease mouse model by increasing oligodendrocyte survival.Nature communications · 2025Article
- ADAR1 editing is necessary for only a small subset of cytosolic dsRNAs to evade MDA5-mediated autoimmunity.Nature genetics · 2025Article
- In Silico Characterization of ADAR1: Structure, Dynamics, and Functional Implications.Current issues in molecular biology · 2025Article
- ADAR1 as a Placental Innate Immune Rheostat Sustaining the Homeostatic Balance of Intrinsic Interferon Response at the Maternal-Fetal Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Smooth muscle expression of RNA editing enzyme ADAR1 controls activation of the RNA sensor MDA5 in atherosclerosis.Nature cardiovascular research · 2025Article
- USP8-Governed MDA5 Homeostasis Promotes Innate Immunity and Autoimmunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The RNA deaminase ADAR1 is an essential negative regulator of the RNA sensor MDA5, and loss of ADAR1 function triggers inappropriate activation of MDA5 by self-RNAs. Mutations in ADAR, the gene that encodes ADAR1, cause human immune diseases, including Aicardi-Goutières syndrome (AGS). However, the mechanisms of MDA5-dependent disease pathogenesis in vivo remain unknown. Here we generated mice with a single amino acid change in ADAR1 that models the most common human ADAR AGS mutation. These Adar mutant mice developed lethal disease that required MDA5, the RIG-I-like receptor LGP2, type I interferons, and the eIF2α kinase PKR. A small-molecule inhibitor of the integrated stress response (ISR) that acts downstream of eIF2α phosphorylation prevented immunopathology and rescued the mice from mortality. These findings place PKR and the ISR as central components of immunopathology in vivo and identify therapeutic targets for treatment of human diseases associated with the ADAR1-MDA5 axis.
Indexed as
Identifiers
What OpenQuestion holds
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.