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

Autoři: Jessica K. Sawyer aff001;  Zahra Kabiri aff001;  Ruth A. Montague aff001;  Scott R. Allen aff002;  Rebeccah Stewart aff001;  Sarah V. Paramore aff001;  Erez Cohen aff002;  Hamed Zaribafzadeh aff001;  Christopher M. Counter aff001;  Donald T. Fox aff001
Působiště autorů: Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, United States of America aff001;  Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, United States of America aff002;  Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, United States of America aff003
Vyšlo v časopise: Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo. PLoS Genet 16(12): e1009228. doi:10.1371/journal.pgen.1009228
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009228


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.

Klíčová slova:

Drosophila melanogaster – ERK signaling cascade – Eyes – Genomic signal processing – MAPK signaling cascades – Ras signaling – Regulator genes – Signal processing


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