Evidence map›Paper›PMID 33296356›Full record

ArticlePLoS genetics2020

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo.

Jessica K Sawyer, Zahra Kabiri, Ruth A Montague, Scott R Allen, Rebeccah Stewart, Sarah V Paramore, Erez Cohen, Hamed Zaribafzadeh, Christopher M Counter, Donald T Fox

Abstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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  3. 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

10 authors.

Jessica K SawyerDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0001-9026-0559
Zahra KabiriDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Ruth A MontagueDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Scott R AllenDepartment of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0002-4809-0493
Rebeccah StewartDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0002-9700-2250
Sarah V ParamoreDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0001-9466-7380
Erez CohenDepartment of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0003-2390-3707
Hamed ZaribafzadehDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Christopher M CounterDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Donald T FoxDepartment of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America.ORCID 0000-0002-0436-179X

Funding

Project 4: The role of codon bias in RAS tumorigenesisP01CA203657 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUNTER, CHRISTOPHER M · 2016 to 2020
$7.9M
TRAINING PROGRAM IN CELL AND MOLECULAR DERMATOLOGYT32AR007197 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JAMES TILFORD ELDER, Sunny Y Wong · 1986 to 2026
$4.2M
RalA signal transductionR01CA094184 · NCI · DUKE UNIVERSITY · PI COUNTER, CHRISTOPHER M · 2002 to 2018
$4.1M
Examining infection-mediated metastasis with single-cell resolutionF32GM109538 · NIGMS · DUKE UNIVERSITY · PI SAWYER, JESSICA KIMBERLEY · 2014 to 2015
$113k
NCI NIH HHS P01 CA203657NCI NIH HHS R01 CA094184NIAMS NIH HHS T32 AR007197NIGMS NIH HHS F32 GM109538
6 · The paper itself

Abstract

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. Our screen enriched for regions of the genome not previously connected with Ras phenotypic modification. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. In multiple contexts, we show that RpS21 preferentially influences weak Ras/MAPK signaling outputs. These data show that codon usage manipulation can identify new, output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.

Indexed as

Codon UsageGenes, ModifierAnimalsDrosophila melanogasterDrosophila ProteinsMAP Kinase Signaling SystemMitogen-Activated Protein Kinasesras ProteinsDrosophila ProteinsMitogen-Activated Protein Kinasesras Proteins

Identifiers

PMID33296356
PMCPMC7752094

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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.