Evidence map›Paper›PMID 30270105›Full record

ArticleMolecular cell2018

RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization.

Swapnil C Devarkar, Brandon Schweibenz, Chen Wang, Joseph Marcotrigiano, Smita S Patel

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 83 citations in OpenAlex.

  1. Review
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  10. 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 · 2025
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  13. Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024
    Review
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  16. eLife · 2024
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  17. Review
  18. Hachiman is a genome integrity sensor.bioRxiv : the preprint server for biology · 2024
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  19. bioRxiv : the preprint server for biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Swapnil C DevarkarDepartment of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Brandon SchweibenzDepartment of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
Chen WangLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Joseph MarcotrigianoLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: joseph.marcotrigiano@nih.gov.
Smita S PatelDepartment of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: patelss@rwjms.rutgers.edu.
Johnson University · USNational Institute of Allergy and Infectious Diseases · USRutgers, The State University of New Jersey · US

Funding

Mechanistic studies of nucleic acid enzymes involved in DNA replication, transcription, and innate immunity.R35GM118086 · NIGMS · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI SMITA S PATEL · 2016 to 2026
$8.9M
Discrimination of nonself by innate immune receptorsZIAAI001218 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MARCOTRIGIANO, JOSEPH · 2017 to 2021
$4.0M
Structural and mechanistic studies of self and non-self recognition by RIG-IR01GM111959 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI BREWER, GARY A., PATEL, SMITA S · 2014 to 2017
$1.8M
NIGMS NIH HHS R01 GM111959NIGMS NIH HHS R35 GM118086
6 · The paper itself

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.

Indexed as

Adenosine TriphosphatasesAdenosine TriphosphateAortic DiseasesCell LineDEAD Box Protein 58DEAD-box RNA HelicasesDental Enamel HypoplasiaFemaleHEK293 CellsHumansHydrolysisKineticsMetacarpusMuscular DiseasesOdontodysplasiaOsteoporosisAdenosine TriphosphatasesAdenosine TriphosphateDEAD Box Protein 58DEAD-box RNA HelicasesReceptors, Antigen, T-CellReceptors, ImmunologicRIGI protein, humanRNARNA, Double-StrandedATPinnate immunitykinetic proofreadingkineticsoligomerizationRIG-IRNA discriminationself-versus-non-selftranslocation

Identifiers

PMID30270105
PMCPMC6434538
OpenAlexW2892732519

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.