Evidence map›Paper›PMID 28760879›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2017

PACT Facilitates RNA-Induced Activation of MDA5 by Promoting MDA5 Oligomerization.

Pak-Yin Lui, Lok-Yin Roy Wong, Ting-Hin Ho, Shannon Wing Ngor Au, Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04934111 (A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid), which is not on this map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.3field-weighted citation impact, top 11% 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.

NCT04934111 phase1unknown statusnot on this mapstarted 2021, after this paper: background citation

A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid (saRNA) Vaccine, in SARS-CoV-2 Seronegative and Seropositive Uganda Population

TypeinterventionalSponsorMRC/UVRI and LSHTM Uganda Research UnitRan2021 to 2022Enrolled42ConditionsCOVID-19ArmsLNP-nCOV saRNA-02 Vaccine
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 50 citations in OpenAlex.

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  11. DYT-Biomolecules · 2022
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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 2 countries.

Pak-Yin LuiSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0003-2879-604X
Lok-Yin Roy WongSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0002-0727-8289
Ting-Hin HoSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Shannon Wing Ngor AuSchool of Life Sciences, Chinese University of Hong Kong, Shatin, Hong Kong; and.
Chi-Ping ChanSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Kin-Hang KokShenzhen Institute of Research and Innovation, The University of Hong Kong, Nanshan, Shenzhen, China 518057; khkok@hku.hk dyjin@hku.hk.ORCID 0000-0003-3426-332X
Dong-Yan JinSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong; khkok@hku.hk dyjin@hku.hk.ORCID 0000-0002-2778-3530
City University of Hong Kong, Shenzhen Research Institute · CNChinese University of Hong Kong · HK

Funding

TRAINING IN MECHANISMS OF PARASITISMT32AI007511 · NIAID · UNIVERSITY OF IOWA · PI BUTLER, NOAH SULLIVAN, WEBER, MARY · 1996 to 2025
$8.1M
NIAID NIH HHS T32 AI007511
6 · The paper itself

Abstract

MDA5 is a RIG-I-like cytoplasmic sensor of dsRNA and certain RNA viruses, such as encephalomyocarditis virus, for the initiation of the IFN signaling cascade in the innate antiviral response. The affinity of MDA5 toward dsRNA is low, and its activity becomes optimal in the presence of unknown cellular coactivators. In this article, we report an essential coactivator function of dsRNA-binding protein PACT in mediating the MDA5-dependent type I IFN response. Virus-induced and polyinosinic-polycytidylic acid-induced activation of MDA5 were severely impaired in PACT-knockout cells and attenuated in PACT-knockdown cells, but they were potentiated when PACT was overexpressed. PACT augmented IRF3-dependent type I IFN production subsequent to dsRNA-induced activation of MDA5. In contrast, PACT had no influence on MDA5-mediated activation of NF-κB. PACT required dsRNA interaction for its action on MDA5 and promoted dsRNA-induced oligomerization of MDA5. PACT had little stimulatory effect on MDA5 mutants deficient for oligomerization and filament assembly. PACT colocalized with MDA5 in the cytoplasm and potentiated MDA5 recruitment to the dsRNA ligand. Taken together, these findings suggest that PACT functions as an essential cellular coactivator of RIG-I, as well as MDA5, and it facilitates RNA-induced formation of MDA5 oligomers.

Indexed as

Cardiovirus InfectionsClustered Regularly Interspaced Short Palindromic RepeatsEncephalomyocarditis virusGene Knockdown TechniquesHEK293 CellsHumansImmunity, InnateInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-3Interferon Type IMutationPoly I-CPolymerizationRNA-Binding ProteinsRNA, Double-StrandedIFIH1 protein, humanInterferon-Induced Helicase, IFIH1Interferon Regulatory Factor-3Interferon Type IIRF3 protein, humanPoly I-CPRKRA protein, humanRNA-Binding ProteinsRNA, Double-Stranded

Identifiers

PMID28760879
PMCPMC9202335
OpenAlexW2740482014

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.