Evidence map›Paper›PMID 38375914›Full record

ArticleNucleic acids research2024

A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.

Divya Kolakada, Amy E Campbell, Laura Baquero Galvis, Zhongyou Li, Mlana Lore, Sujatha Jagannathan

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Divya KolakadaMolecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Amy E CampbellDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Laura Baquero GalvisDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Zhongyou LiDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Mlana LoreMolecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Sujatha JagannathanDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.ORCID 0000-0001-9039-2631

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
Understanding the variability in nonsense-mediated RNA decayR35GM133433 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Sujatha Jagannathan · 2019 to 2026
$3.1M
Mechanisms of DUX4-induced misregulation of RNA processing and quality controlR01AR083381 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI Sujatha Jagannathan · 2024 to 2026
$1.5M
NCI NIH HHS P30 CA046934NIAMS NIH HHS R01 AR083381NIGMS NIH HHS R35 GM133433NIGMS NIH HHS T32 GM136444NIH HHS R35GM133433
6 · The paper itself

Abstract

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and an NMD inhibitor (SMG1i), alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.

Indexed as

ExonsGenes, ReporterGenetic TechniquesNonsense Mediated mRNA DecayHEK293 CellsHumansRNA, MessengerRNA, Messenger

Identifiers

PMID38375914
PMCPMC11014337

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Registered trials

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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.