Evidence map›Paper›PMID 35024243›Full record

ArticleMolecular therapy. Nucleic acids2022

Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay.

Jingrong Zhao, Zhelin Li, Ruchira Puri, Kelvin Liu, Israel Nunez, Liang Chen, Sika Zheng

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 34 citations in OpenAlex.

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  13. Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024
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  16. Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
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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 1 country.

Jingrong ZhaoDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
Zhelin LiDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
Ruchira PuriDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
Kelvin LiuDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
Israel NunezDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
Liang ChenDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Sika ZhengDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 91709, USA.
University of California, Riverside · USUniversity of Southern California · US

Funding

The Role of NMD in Cortical Neural Progenitor CellsR01NS125276 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Sika Zheng · 2022 to 2026
$2.6M
RNA regulation of intrinsically-determined neuronal propertiesR01MH116220 · NIMH · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI ZHENG, SIKA · 2018 to 2022
$2.4M
The Regulation and Function of Neuron-Specific Alternative SplicingR01NS104041 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI ZHENG, SIKA · 2018 to 2022
$2.1M
Understanding the NMD regulatory path from genetic variation to phenotypesR01GM137428 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, LIANG · 2020 to 2023
$1.6M
NIGMS NIH HHS R01 GM137428NIMH NIH HHS R01 MH116220NINDS NIH HHS R01 NS104041NINDS NIH HHS R01 NS125276
6 · The paper itself

Abstract

Nonsense-mediated mRNA decay (NMD) degrades transcripts with premature stop codons. Given the prevalence of nonsense single nucleotide polymorphisms (SNPs) in the general population, it is urgent to catalog the effects of clinically approved drugs on NMD activity: any interference could alter the expression of nonsense SNPs, inadvertently inducing adverse effects. This risk is higher for patients with disease-causing nonsense mutations or an illness linked to dysregulated nonsense transcripts. On the other hand, hundreds of disorders are affected by cellular NMD efficiency and may benefit from NMD-modulatory drugs. Here, we profiled individual FDA-approved drugs for their impact on cellular NMD efficiency using a sensitive method that directly probes multiple endogenous NMD targets for a robust readout of NMD modulation. We found most FDA-approved drugs cause unremarkable effects on NMD, while many elicit clear transcriptional responses. Besides several potential mild NMD modulators, the anticancer drug homoharringtonine (HHT or omacetaxine mepesuccinate) consistently upregulates various endogenous NMD substrates in a dose-dependent manner in multiple cell types. We further showed translation inhibition mediates HHT's NMD effect. In summary, many FDA drugs induce transcriptional changes, and a few impact global NMD, and direct measurement of endogenous NMD substrate expression is robust to monitor cellular NMD.

Indexed as

albendazoleartesunategabexate mesilateHnrnplmitoxantronemontelukast sodiumPtbp2topotecan hydrochlorideTra2btrazodone hydrochloride

Identifiers

PMID35024243
PMCPMC8718828
OpenAlexW4200276717

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.