Evidence map›Paper›PMID 34021034›Full record

ArticleGut2022

RNA helicase DDX5 enables STAT1 mRNA translation and interferon signalling in hepatitis B virus replicating hepatocytes.

Jiazeng Sun, Guanhui Wu, Florentin Pastor, Naimur Rahman, Wen-Hung Wang, Zhengtao Zhang, Philippe Merle, Lijian Hui, Anna Salvetti, David Durantel and 2 more

Open access · greenAbstract read
In one paragraph

Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
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  6. Human lncRNAProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Review
  8. Article
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  12. Article
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  14. ATRA upregulates OTUD6B to recruit CD8Cell death & disease · 2025
    Article
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  16. Review
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  18. Review
  19. Review
  20. Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
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

12 authors at 4 institutions in 3 countries.

Jiazeng SunBasic Medical Sciences, Purdue University, West Lafayette, Indiana, USA.
Guanhui Wu *Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Florentin Pastor *International Center for Infectiology Research (CIRI), INSERM U1111-CNRS UMR5308, Lyon, France.
Naimur RahmanBasic Medical Sciences, Purdue University System, West Lafayette, Indiana, USA.
Wen-Hung WangGene Editing Core, Bindley Biosciences Center, Purdue University, West Lafayette, Indiana, USA.
Zhengtao ZhangDepartment of Biochemistry and Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Philippe MerleService d'Hépatologie, Hôpital de La Croix-Rousse Centre Livet, Lyon, Rhône-Alpes, France.
Lijian HuiDepartment of Biochemistry and Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
Anna SalvettiInternational Center for Infectiology Research (CIRI), INSERM U1111-CNRS UMR5308, Lyon, France.
David DurantelINSERM U1111-CNRS UMR5308 International Center for Infectiology Research (CIRI), Lyon, France.ORCID 0000-0002-9226-3419
Danzhou YangDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.ORCID 0000-0001-7489-7111
Ourania AndrisaniBasic Medical Sciences, Purdue University, West Lafayette, Indiana, USA andrisao@purdue.edu.ORCID 0000-0002-6230-0303
Purdue University West Lafayette · USUniversité Claude Bernard Lyon 1 · FRCenter for Excellence in Molecular Cell Science · CNHôpital de la Croix-Rousse · FR

Funding

Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI Andrea L Kasinski · 1985 to 2026
$43.4M
INDIANA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (UL1): BPCAUL1RR025761 · NCRR · INDIANA UNIVERSITY INDIANAPOLIS · PI SHEKHAR, ANANTHA · 2008 to 2011
$21.0M
Role of CREB/ATF Proteins in Hepatocyte Growth ControlR01DK044533 · NIDDK · PURDUE UNIVERSITY WEST LAFAYETTE · PI ANDRISANI, OURANIA M. · 1999 to 2021
$5.1M
Targeting MYC promoter G-quadruplex for MYC inhibition by IndenoisoquinolinesR01CA177585 · NCI · UNIVERSITY OF ARIZONA · PI SINTIM, HERMAN O, YANG, DANZHOU · 2014 to 2025
$4.0M
Nucleolin recognition of MYC promoter G-quadruplex and its role in MYC regulation by MycG4-ligandsU01CA240346 · NCI · PURDUE UNIVERSITY · PI YANG, DANZHOU · 2020 to 2024
$2.1M
NCI NIH HHS P30 CA023168NCI NIH HHS R01 CA177585NCI NIH HHS U01 CA240346NCRR NIH HHS UL1 RR025761NIDDK NIH HHS R01 DK044533
6 · The paper itself

Abstract

objectiveRNA helicase DDX5 is downregulated during HBV replication and poor prognosis HBV-related hepatocellular carcinoma (HCC). The objective of this study is to investigate the role of DDX5 in interferon (IFN) signalling. We provide evidence of a novel mechanism involving DDX5 that enables translation of transcription factor STAT1 mediating the IFN response. DESIGN AND

resultsMolecular, pharmacological and biophysical assays were used together with cellular models of HBV replication, HCC cell lines and liver tumours. We demonstrate that DDX5 regulates STAT1 mRNA translation by resolving a G-quadruplex (rG4) RNA structure, proximal to the 5' end of STAT1 5'UTR. We employed luciferase reporter assays comparing wild type (WT) versus mutant rG4 sequence, rG4-stabilising compounds, CRISPR/Cas9 editing of the STAT1-rG4 sequence and circular dichroism determination of the rG4 structure. STAT1-rG4 edited cell lines were resistant to the effect of rG4-stabilising compounds in response to IFN-α, while HCC cell lines expressing low DDX5 exhibited reduced IFN response. Ribonucleoprotein and electrophoretic mobility assays demonstrated direct and selective binding of RNA helicase-active DDX5 to the WT STAT1-rG4 sequence. Immunohistochemistry of normal liver and liver tumours demonstrated that absence of DDX5 corresponded to absence of STAT1. Significantly, knockdown of DDX5 in HBV infected HepaRG cells reduced the anti-viral effect of IFN-α.

conclusionRNA helicase DDX5 resolves a G-quadruplex structure in 5'UTR of STAT1 mRNA, enabling STAT1 translation. We propose that DDX5 is a key regulator of the dynamic range of IFN response during innate immunity and adjuvant IFN-α therapy.

Indexed as

Carcinoma, HepatocellularLiver Neoplasms5' Untranslated RegionsAntiviral AgentsDEAD-box RNA HelicasesHepatitis B virusHepatocytesHumansInterferon-alphaProtein BiosynthesisRNA HelicasesSTAT1 Transcription FactorVirus Replication5' Untranslated RegionsAntiviral AgentsDdx5 protein, humanDEAD-box RNA HelicasesInterferon-alphaRNA HelicasesSTAT1 protein, humanSTAT1 Transcription Factorhepatitis Bhepatocellular carcinomahepatocyteinterferon-alphamolecular mechanisms

Identifiers

PMID34021034
PMCPMC8606016
OpenAlexW3163562866

What OpenQuestion holds

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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.