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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Sawyer, JK; Kabiri, Z; Montague, RA; Allen, SR; Stewart, R; Paramore, SV; Cohen, E; Zaribafzadeh, H; Counter, CM; Fox, DT

Published Date

  • December 2020

Published In

Volume / Issue

  • 16 / 12

Start / End Page

  • e1009228 -

PubMed ID

  • 33296356

Pubmed Central ID

  • PMC7752094

Electronic International Standard Serial Number (EISSN)

  • 1553-7404

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1009228


  • eng

Conference Location

  • United States