Evidence map›Paper›PMID 39384561›Full record

ArticleScientific reports2024

Activation of PKR by a short-hairpin RNA.

Kyle A Cottrell, Sua Ryu, Helen Donelick, Hung Mai, Addison A Young, Jackson R Pierce, Brenda L Bass, Jason D Weber

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. BRAFbioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Kyle A Cottrell *Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO, 63110, USA. cottrellka@pudue.edu.
Sua Ryu *Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO, 63110, USA.
Helen DonelickDepartment of Biochemistry, University of Utah, Salt Lake City, UT, USA.
Hung MaiDepartment of Medicine, Division of Molecular Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO, 63110, USA.
Addison A YoungDepartment of Biochemistry, Purdue University, S University St, West Lafayette, IN, 201, USA.
Jackson R PierceDepartment of Biochemistry, Purdue University, S University St, West Lafayette, IN, 201, USA.
Brenda L BassDepartment of Biochemistry, University of Utah, Salt Lake City, UT, USA.
Jason D WeberDepartment of Medicine, Division of Molecular Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St. Louis, MO, 63110, USA. jweber@wustl.edu.

Funding

Elucidating roles and mechanisms of double-stranded RNA-mediated pathwaysR35GM141262 · NIGMS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Brenda L. Bass · 2021 to 2026
$3.7M
Antagonistic role of ARF and ADAR1 in triple-negative breast cancerR01CA262804 · NCI · WASHINGTON UNIVERSITY · PI Jason Weber · 2022 to 2026
$2.1M
Identifying determinants of ADAR-dependency in triple-negative breast cancerR00MD016946 · NIMHD · PURDUE UNIVERSITY · PI COTTRELL, KYLE · 2023 to 2025
$722k
Identifying determinants of ADAR-dependency in triple-negative breast cancerK99MD016946 · NIMHD · WASHINGTON UNIVERSITY · PI COTTRELL, KYLE · 2022 to 2023
$108k
National Institutes of Health, Pakistan R01CA262804NCI NIH HHS R01 CA262804NIGMS NIH HHS R35 GM141262NIH HHS K99MD016946NIH HHS R35GM141262NIMHD NIH HHS K99 MD016946NIMHD NIH HHS R00 MD016946
6 · The paper itself

Abstract

Recognition of viral infection often relies on the detection of double-stranded RNA (dsRNA), a process that is conserved in many different organisms. In mammals, proteins such as MDA5, RIG-I, OAS, and PKR detect viral dsRNA, but struggle to differentiate between viral and endogenous dsRNA. This study investigates an shRNA targeting DDX54's potential to activate PKR, a key player in the immune response to dsRNA. Knockdown of DDX54 by a specific shRNA induced robust PKR activation in human cells, even when DDX54 is overexpressed, suggesting an off-target mechanism. Activation of PKR by the shRNA was enhanced by knockdown of ADAR1, a dsRNA binding protein that suppresses PKR activation, indicating a dsRNA-mediated mechanism. In vitro assays confirmed direct PKR activation by the shRNA. These findings emphasize the need for rigorous controls and alternative methods to validate gene function and minimize unintended immune pathway activation.

Indexed as

eIF-2 KinaseRNA-Binding ProteinsRNA, Double-StrandedRNA, Small InterferingAdenosine DeaminaseDEAD-box RNA HelicasesEnzyme ActivationGene Knockdown TechniquesHEK293 CellsHumansADAR protein, humanAdenosine DeaminaseDEAD-box RNA HelicasesEIF2AK2 protein, humaneIF-2 KinaseRNA-Binding ProteinsRNA, Double-StrandedRNA, Small InterferingDouble-stranded RNAdsRNAPKRRNAiRNA interference

Identifiers

PMID39384561
PMCPMC11464672

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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.