ArticleNucleic acids research2016
The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Terminal loop sequences in viral double-stranded RNAs modulate RIG-I signaling.RNA (New York, N.Y.) · 2026Article
- 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
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
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- Article
- Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2.Nucleic acids research · 2024Article
- Characterization of RNA driven structural changes in full length RIG-I leading to its agonism or antagonism.Nucleic acids research · 2023Article
- RIG-I recognizes metabolite-capped RNAs as signaling ligands.Nucleic acids research · 2023Article
- Structural Insights into the Advances and Mechanistic Understanding of Human Dicer.Biochemistry · 2023Review
- Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity.Molecular therapy. Nucleic acids · 2022Article
- A loosened gating mechanism of RIG-I leads to autoimmune disorders.Nucleic acids research · 2022Article
- The intrinsically disordered CARDs-Helicase linker in RIG-I is a molecular gate for RNA proofreading.The EMBO journal · 2022Article
- The molecular mechanism of RIG-I activation and signaling.Immunological reviews · 2021Review
- Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3).Nucleic acids research · 2021Article
- Review
- The influenza NS1 protein modulates RIG-I activation via a strain-specific direct interaction with the second CARD of RIG-I.The Journal of biological chemistry · 2020Article
- RNA binding activates RIG-I by releasing an autorepressed signaling domain.Science advances · 2019Article
- HDX-MS reveals dysregulated checkpoints that compromise discrimination against self RNA during RIG-I mediated autoimmunity.Nature communications · 2018Article
- RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.Molecular cell · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal.
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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.