ArticleImmunity2012
Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response.
Article in Immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 274 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
274 citing papers in PubMed, 391 citations in OpenAlex.
- DZIP3 is a viral RNA co-sensor for RIG-I that promotes type-I interferon responses.The EMBO journal · 2026Article
- A designed ubiquitin-binding protein selectively enriches and visualizes unanchored ubiquitin.Science advances · 2026Article
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- Transcriptomic Evidence of Mitochondrial Double-Stranded RNA Accumulation in Brain Aging and Alzheimer's Disease.Aging cell · 2026Article
- Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- RNF213 Is an Interferon-Stimulated Gene That Targets Influenza A Virus NP and Activates MDA5 to Restrict Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- Nairobi sheep disease virus: an emerging threat with unresolved pathogenesis and zoonotic potential.Journal of virology · 2026Review
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- Long Non-Coding RNAs Can Govern the Antiviral Immune Response Through Interferon-Mediated Mechanisms in Respiratory Tract.Viruses · 2026Review
- Mitochondrial double-stranded RNA accumulation in brain aging and Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- CDK10 suppresses nucleic acid sensors-mediated antitumor immunity.Nature cancer · 2026Article
- Unanchored K63-linked polyubiquitin chains: a novel second messenger involved in G protein-coupled receptors early signaling events.Cell communication and signaling : CCS · 2026Article
- Characterization of RNA interference in the cnidarian Nematostella vectensis reveals partial target silencing but lack of small RNA amplification.PLoS biology · 2026Article
- Review
- The integrin protein ITGβ1 effectively suppresses porcine epidemic diarrhea virus replication through facilitating MDA5 oligomerization and subsequent activation of the type I interferon signaling pathway.Journal of virology · 2025Article
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- A diverse family of bacterial deubiquitinases is defined by theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
214 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
RIG-I and MDA5 detect viral RNA in the cytoplasm and activate signaling cascades leading to the production of type-I interferons. RIG-I is activated through sequential binding of viral RNA and unanchored lysine-63 (K63) polyubiquitin chains, but how polyubiquitin activates RIG-I and whether MDA5 is activated through a similar mechanism remain unresolved. Here, we showed that the CARD domains of MDA5 bound to K63 polyubiquitin and that this binding was essential for MDA5 to activate the transcription factor IRF3. Mutations of conserved residues in MDA5 and RIG-I that disrupt their ubiquitin binding also abrogated their ability to activate IRF3. Polyubiquitin binding induced the formation of a large complex consisting of four RIG-I and four ubiquitin chains. This hetero-tetrameric complex was highly potent in activating the antiviral signaling cascades. These results suggest a unified mechanism of RIG-I and MDA5 activation and reveal a unique mechanism by which ubiquitin regulates cell signaling and immune response.
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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.