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

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Genetics, Vol 16, Iss 12, p e1009228 (2020)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1009228
Popis: 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.
Databáze: Directory of Open Access Journals