ArticleCell2010
Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity.
Article in Cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 400 papers, 1 of them a synthesis that pooled it.
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
400 citing papers in PubMed, 1 synthesis or guideline pooled it, 597 citations in OpenAlex.
- To TRIM the Immunity: From Innate to Adaptive Immunity.Frontiers in immunology · 2020Pooled it
- 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
- miR-26a-5p Activates Antiviral Innate Immunity via Direct Binding and Activation of RIG-I.Viruses · 2026Article
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- An ancient anthozoan protein reveals an alternative evolutionary path of antiviral signalling.Nature ecology & evolution · 2026Article
- TRIM28 and TRIM32: multifaceted regulators of innate immunity and antiviral defence.Immunologic research · 2026Review
- Emerging Role and Potential Therapeutic Application of TRIM Proteins in Cardiovascular Diseases.Biomolecules · 2026Review
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- CSDE1 promotes viral immune evasion through RNA-dependent and phosphorylation-modulated liquid-liquid phase separation.Nature communications · 2026Article
- Histone Demethylase JMJD2D Suppresses Influenza A Virus Infection by Promoting RIG-I Expression.Biomolecules · 2026Article
- TRIM13 Positively Regulates the NF-κB Signaling Pathway Induced by Encephalomyocarditis Virus.Viruses · 2026Article
- NSP1 of Alongshan virus antagonizes type I interferon responses by promoting STUB1-mediated degradation of RIG-I.Cell communication and signaling : CCS · 2026Article
- The Crohn's disease-related RNF123 prevents NLRP3 inflammasome assembly by catalyzing unanchored K63-linked ubiquitination on NEK7.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Prion-like MAVS fibrils stitch mitochondria to promote a rapid antiviral response.Cellular & molecular immunology · 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
- Intrinsic OASL expression governs heterogeneity in interferon induction during influenza A virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
340 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
RIG-I detects invading viral RNA and activates the transcription factors NF-kappaB and IRF3 through the mitochondrial protein MAVS. Here we show that RNA bearing 5'-triphosphate strongly activates the RIG-I-IRF3 signaling cascade in a reconstituted system composed of RIG-I, mitochondria, and cytosol. Activation of RIG-I requires not only RNA but also polyubiquitin chains linked through lysine 63 (K63) of ubiquitin. RIG-I binds specifically to K63-polyubiquitin chains through its tandem CARD domains in a manner that depends on RNA and ATP. Mutations in the CARD domains that abrogate ubiquitin binding also impair RIG-I activation. Remarkably, unanchored K63-ubiquitin chains, which are not conjugated to any target protein, potently activate RIG-I. These ubiquitin chains function as an endogenous ligand of RIG-I in human cells. Our results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity.
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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.