ArticleCell2018
Breaching Self-Tolerance to Alu Duplex RNA Underlies MDA5-Mediated Inflammation.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 290 papers.
What it found
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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.
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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
290 citing papers in PubMed, 440 citations in OpenAlex.
- Reading the SINEs - functionality in noncoding RNA 'cheap genes'.RNA biology · 2026Review
- dsRNAscan maps human dsRNAome, revealing conservation, intermolecular dsRNA, and correlates of ADAR dependency.Molecular cell · 2026Article
- Extracellular RNA clearance by non-canonical cell-surface MDA5 protects against lung fibrosis.EMBO molecular medicine · 2026Article
- Establishing the molecular basis for MDA5 mutation-linked autoimmunity.Nucleic acids research · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- 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
- LINE-1 Epigenetic Repression and Regulation of Immunity.Viruses · 2026Review
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- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Promoter-associated RNA polymerase III shapes RNA polymerase II-dependent inflammatory gene expression during viral infection.bioRxiv : the preprint server for biology · 2026Article
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- MDA5 and the integrated stress response control sex-specific type 1 diabetes onset in NOD mice.bioRxiv : the preprint server for biology · 2026Article
- Quantitative Control of Transposable Elements: From Genome Plasticity to Immune Regulatory Circuits.Cell biochemistry and function · 2026Review
- The regulatory mechanism and clinical significance of RNA editing in prostate cancer.Current urology · 2026Review
- A cytoplasmic index for quantifying immune-related A-to-I RNA editing.Genome biology · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- mNature communications · 2026Article
- Tumour-associated high endothelial venules drive portal-specific immune evasion in lymph nodes via ALOX12.Nature communications · 2026Article
230 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral dsRNA sensor that induces antiviral immune response. Using a newly developed RNase-protection/RNA-seq approach, we demonstrate here that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNAs because of its limited filament formation on imperfect duplexes, AGS variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNAs. Moreover, we identified an unexpected role of an RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context dependence of self versus non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 in recognizing dsRNA comes at a cost of self-recognition and implicates a unique role of Alu-dsRNAs as virus-like elements that shape the primate immune system.
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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.