ArticleMolecular cell2018
RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 83 citations in OpenAlex.
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- Human RIG-I Antiviral Deficiency Caused by a Dominant-Negative Variant Locked in a Signaling-Inactive State.medRxiv : the preprint server for health sciences · 2026Article
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Febrile temperature activates the innate immune response by promoting aberrant influenza A virus RNA synthesis.Science advances · 2026Article
- An autoinflammatory RIG-I variant causing Singleton-Merten syndrome associates with small non-coding Y-RNAs.Discovery immunology · 2026Article
- LGP2 stops MDA5 translocation to start antiviral signaling.Cell research · 2025Article
- Toward unraveling molecular grammars for dsRNA-binding proteins: substrate recognition to binding mechanisms.BMB reports · 2025Review
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- Febrile temperature activates the innate immune response by promoting aberrant influenza A virus RNA synthesis.bioRxiv : the preprint server for biology · 2025Article
- Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing.Nature cell biology · 2025Article
- Influenza virus antagonizes self sensing by RIG-I to enhance viral replication.bioRxiv : the preprint server for biology · 2025Article
- Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024Review
- Article
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Article
- The molecular language of RNA 5' ends: guardians of RNA identity and immunity.RNA (New York, N.Y.) · 2024Review
- Hachiman is a genome integrity sensor.bioRxiv : the preprint server for biology · 2024Article
- Article
- The NS1 protein of influenza B virus binds 5'-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
RIG-I has a remarkable ability to specifically select viral 5'ppp dsRNAs for activation from a pool of cytosolic self-RNAs. The ATPase activity of RIG-I plays a role in RNA discrimination and activation, but the underlying mechanism was unclear. Using transient-state kinetics, we elucidated the ATPase-driven "kinetic proofreading" mechanism of RIG-I activation and RNA discrimination, akin to DNA polymerases, ribosomes, and T cell receptors. Even in the autoinhibited state of RIG-I, the C-terminal domain kinetically discriminates against self-RNAs by fast off rates. ATP binding facilitates dsRNA engagement but, interestingly, makes RIG-I promiscuous, explaining the constitutive signaling by Singleton-Merten syndrome-linked mutants that bind ATP without hydrolysis. ATP hydrolysis dissociates self-RNAs faster than 5'ppp dsRNA but, more importantly, drives RIG-I oligomerization through translocation, which we show to be regulated by helicase motif IVa. RIG-I translocates directionally from the dsRNA end into the stem region, and the 5'ppp end "throttles" translocation to provide a mechanism for threading and building a signaling-active oligomeric complex.
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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.