Evidence map›Paper›PMID 27928057›Full record

ArticleNucleic acids research2017

Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication.

Lulzim Shkreta, Marco Blanchette, Johanne Toutant, Emmanuelle Wilhelm, Brendan Bell, Benjamin A Story, Ahalya Balachandran, Alan Cochrane, Peter K Cheung, P Richard Harrigan and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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.

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

34 citing papers in PubMed, 47 citations in OpenAlex.

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  16. HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency.Frontiers in cellular and infection microbiology · 2022
    Review
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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 5 institutions in 2 countries.

Lulzim ShkretaDepartment of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Marco BlanchetteStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Johanne ToutantDepartment of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Emmanuelle WilhelmDepartment of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Brendan BellDepartment of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Benjamin A StoryStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Ahalya BalachandranDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Alan CochraneDepartment of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Peter K CheungBC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
P Richard HarriganBC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
David S GriersonFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Benoit ChabotDepartment of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1E 4K8, Canada.
Université de Sherbrooke · CAStowers Institute for Medical Research · USUniversity of British Columbia · CAUniversity of Toronto · CAAIDS Vancouver · CA

Funding

SPORE in Gastrointestinal CancerP50CA095060 · NCI · UNIVERSITY OF ARIZONA · PI GERNER, EUGENE W · 2002 to 2012
$25.3M
CIHRNCI NIH HHS P50 CA095060
6 · The paper itself

Abstract

We recently identified the 4-pyridinone-benzisothiazole carboxamide compound 1C8 as displaying strong anti-HIV-1 potency against a variety of clinical strains in vitro. Here we show that 1C8 decreases the expression of HIV-1 and alters splicing events involved in the production of HIV-1 mRNAs. Although 1C8 was designed to be a structural mimic of the fused tetracyclic indole compound IDC16 that targets SRSF1, it did not affect the splice site shifting activity of SRSF1. Instead, 1C8 altered splicing regulation mediated by SRSF10. Depleting SRSF10 by RNA interference affected viral splicing and, like 1C8, decreased expression of Tat, Gag and Env. Incubating cells with 1C8 promoted the dephosphorylation of SRSF10 and increased its interaction with hTra2β, a protein previously implicated in the control of HIV-1 RNA splicing. While 1C8 affects the alternative splicing of cellular transcripts controlled by SRSF10 and hTra2β, concentrations greater than those needed to inhibit HIV-1 replication were required to elicit significant alterations. Thus, the ability of 1C8 to alter the SRSF10-dependent splicing of HIV-1 transcripts, with minor effects on cellular splicing, supports the view that SRSF10 may be used as a target for the development of new anti-viral agents.

Indexed as

Alternative SplicingAnti-HIV AgentsBenzothiazolesCell Cycle ProteinsCells, CulturedHeLa CellsHIV-1HumansNiacinamideRepressor ProteinsRNA, MessengerRNA PrecursorsRNA Splicing FactorsSerine-Arginine Splicing FactorsTranscription, GeneticVirus Replication1C8 compoundAnti-HIV AgentsBenzothiazolesCell Cycle ProteinsNiacinamideRepressor ProteinsRNA, MessengerRNA PrecursorsRNA Splicing FactorsSerine-Arginine Splicing FactorsSRSF10 protein, human

Identifiers

PMID27928057
PMCPMC5397194
OpenAlexW2578821355

What OpenQuestion holds

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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.