ArticleThe EMBO journal2022
The intrinsically disordered CARDs-Helicase linker in RIG-I is a molecular gate for RNA proofreading.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- 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
- Review
- An autoinflammatory RIG-I variant causing Singleton-Merten syndrome associates with small non-coding Y-RNAs.Discovery immunology · 2026Article
- The RIG-I-like receptor family of immune proteins.Molecular cell · 2025Review
- Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing.Nature cell biology · 2025Article
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2.Nucleic acids research · 2024Article
- An intracellular bacterial pathogen triggers RIG-I/MDA5-dependent necroptosis.Current research in microbial sciences · 2024Article
- Protein disorder and autoinhibition: The role of multivalency and effective concentration.Current opinion in structural biology · 2023Review
- A conserved isoleucine in the binding pocket of RIG-I controls immune tolerance to mitochondrial RNA.Nucleic acids research · 2023Article
- RIG-I recognizes metabolite-capped RNAs as signaling ligands.Nucleic acids research · 2023Article
- Friend or foe: RIG- I like receptors and diseases.Autoimmunity reviews · 2022Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The innate immune receptor RIG-I provides a first line of defense against viral infections. Viral RNAs are recognized by RIG-I's C-terminal domain (CTD), but the RNA must engage the helicase domain to release the signaling CARD (Caspase Activation and Recruitment Domain) domains from their autoinhibitory CARD2:Hel2i interactions. Because the helicase itself lacks RNA specificity, mechanisms to proofread RNAs entering the helicase domain must exist. Although such mechanisms would be crucial in preventing aberrant immune responses by non-specific RNAs, they remain largely uncharacterized to date. This study reveals a previously unknown proofreading mechanism through which RIG-I ensures that the helicase engages RNAs explicitly recognized by the CTD. A crucial part of this mechanism involves the intrinsically disordered CARDs-Helicase Linker (CHL), which connects the CARDs to the helicase subdomain Hel1. CHL uses its negatively charged regions to antagonize incoming RNAs electrostatically. In addition to this RNA gating function, CHL is essential for stabilization of the CARD2:Hel2i interface. Overall, we uncover that the CHL and CARD2:Hel2i interface work together to establish a tunable gating mechanism that allows CTD-chosen RNAs to bind the helicase domain, while at the same time blocking non-specific RNAs. These findings also indicate that CHL could represent a novel target for RIG-I-based therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.