Evidence map›Paper›PMID 25481564›Full record

ArticleJournal of hepatology2015

The spliceosome factor SART1 exerts its anti-HCV action through mRNA splicing.

Wenyu Lin, Chuanlong Zhu, Jian Hong, Lei Zhao, Nikolaus Jilg, Dahlene N Fusco, Esperance A Schaefer, Cynthia Brisac, Xiao Liu, Lee F Peng and 2 more

Abstract read
In one paragraph

Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 26 citations in OpenAlex.

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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

12 authors at 3 institutions in 1 country.

Wenyu LinLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: wlin1@mgh.harvard.edu.
Chuanlong ZhuLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Infectious Disease, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, China.
Jian HongLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lei ZhaoLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Nikolaus JilgLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Dahlene N FuscoLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Esperance A SchaeferLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Cynthia BrisacLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Xiao LiuLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Lee F PengLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Qikai XuDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Raymond T ChungLiver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: rtchung@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USBrigham and Women's Hospital · US

Funding

Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI GEORG Michael LAUER · 2009 to 2026
$48.1M
Discovery and Assessment of Genetic Determinants of HCV and HIV ControlR01DA033541 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T, KIM, ARTHUR Y · 2011 to 2015
$3.4M
HIV-Hepatitis C Virus Cooperative Interactions and Liver Disease ProgressionR01DK098079 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T · 2013 to 2016
$2.7M
HIV-Hepatitis C Virus Cooperative Interactions and Liver Disease ProgressionR56DK098079 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T · 2012 to 2012
$506k
NIAID NIH HHS AI082630NIAID NIH HHS U19 AI082630NIDA NIH HHS DA033541NIDA NIH HHS R01 DA033541NIDDK NIH HHS DK098079NIDDK NIH HHS R01 DK098079NIDDK NIH HHS R56 DK098079
6 · The paper itself

Abstract

BACKGROUND &/

aimsThe broadly used antiviral cytokine interferon-α (IFNα)'s mechanisms of action against HCV infection are not well understood. We previously identified SART1, a host protein involved in RNA splicing and pre-mRNA processing, as a regulator of IFN's antiviral effects. We hypothesized that SART1 regulates antiviral IFN effector genes (IEGs) through mRNA processing and splicing.

methodsWe performed siRNA knockdown in HuH7.5.1 cells and mRNA-sequencing with or without IFN treatment. Selected gene mRNA variants and their proteins, together with HCV replication, were monitored by qRT-PCR and Western blot in HCV OR6 replicon cells and the JFH1 HCV infectious model.

resultsWe identified 419 genes with a greater than 2-fold expression difference between Neg siRNA and SART1 siRNA treated cells in the presence or absence of IFN. Bioinformatic analysis identified at least 10 functional pathways. SART1 knockdown reduced classical IFN stimulating genes (ISG) mRNA transcription including MX1 and OAS3. However, SART1 did not affect JAK-STAT pathway gene mRNA expression and IFN stimulated response element (ISRE) signaling. We identified alternative mRNA splicing events for several genes, including EIF4G3, GORASP2, ZFAND6, and RAB6A that contribute to their antiviral effects. EIF4G3 and GORASP2 were also confirmed to have anti-HCV effect.

conclusionsThe spliceosome factor SART1 is not IFN-inducible but is an IEG. SART1 exerts its anti-HCV action through direct transcriptional regulation for some ISGs and alternative splicing for others, including EIF4G3, GORASP2. SART1 does not have an effect on IFN receptor or canonical signal transduction components. Thus, SART1 regulates ISGs using a novel, non-classical mechanism.

Indexed as

Hepatitis CInterferon-alphaAntigens, NeoplasmAntiviral AgentsGene Knockdown TechniquesHepacivirusHumansInterferon-Stimulated Gene Factor 3, gamma SubunitRibonucleoproteins, Small NuclearRNA, MessengerRNA, Small InterferingRNA SplicingSignal TransductionSpliceosomesVirus ReplicationAntigens, NeoplasmAntiviral AgentsInterferon-alphaInterferon-Stimulated Gene Factor 3, gamma SubunitRibonucleoproteins, Small NuclearRNA, MessengerRNA, Small InterferingSART1 protein, humanHepatitis C virus (HCV)Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathwayRNA-Sequencing (RNA-Seq)RNA splicingSquamous cell carcinoma antigen recognized by T cells (SART1)

Identifiers

PMID25481564
PMCPMC4404186
OpenAlexW2012634021

What OpenQuestion holds

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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.