Evidence map›Paper›PMID 26612866›Full record

ArticleNucleic acids research2016

The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection.

Anand Ramanathan, Swapnil C Devarkar, Fuguo Jiang, Matthew T Miller, Abdul G Khan, Joseph Marcotrigiano, Smita S Patel

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

30 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  4. eLife · 2024
    Article
  5. 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

7 authors at 2 institutions in 1 country.

Anand RamanathanRobert Wood Johnson Medical School, Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA.
Swapnil C DevarkarRobert Wood Johnson Medical School, Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA.
Fuguo JiangCenter for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Matthew T MillerCenter for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Abdul G KhanCenter for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Joseph MarcotrigianoCenter for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA jmarco@cabm-new.rutgers.edu.
Smita S PatelRobert Wood Johnson Medical School, Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ 08854, USA patelss@rutgers.edu.
Rutgers, The State University of New Jersey · USJohnson University · 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
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
NIAID NIH HHS AI080659NIGMS NIH HHS GM111959NIGMS NIH HHS GM55310NIGMS NIH HHS R01 GM111959NIGMS NIH HHS R35 GM118086
6 · The paper itself

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.

Indexed as

Adenosine TriphosphatasesBase SequenceBinding SitesDEAD Box Protein 58DEAD-box RNA HelicasesFluorescence PolarizationHEK293 CellsHumansInterferon-betaMolecular Sequence DataProtein Structure, TertiaryReceptors, ImmunologicRNARNA, Double-StrandedAdenosine TriphosphatasesDEAD Box Protein 58DEAD-box RNA HelicasesInterferon-betaReceptors, ImmunologicRIGI protein, humanRNARNA, Double-Stranded

Identifiers

PMID26612866
PMCPMC4737149
OpenAlexW2178253322

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.