Date of Completion
Dr. Elaine Lee, Dr. Oh Sung Kwon, Dr. Rachel O'Neill, Dr. Aric Rogers
Field of Study
Master of Science
Environmental stress disrupts cellular homeostasis leading to proteostasis disruptions which must be correct by rapid reprogramming of transcription and translation mediated by the translation machinery of which tRNA and aminoacyl tRNA synthetases are particularly important. Our aim in this study was to conduct a genome-wide RNAi kinase screen of a long-lived and stress-resistant rrt-1(gc47) (MC240) C. elegans mutant that constitutively, under naïve conditions, expresses a GFP reporter for gpdh-1, which is required for survival during hypertonic stress, but not expressed under naïve, non-stress conditions. Our approach was to administer RNAi by feeding, and we used 382 RNAi clones, including genome-wide kinases, to identify kinases required for constitutive expression of gpdh-1 in our MC240 mutant under naïve conditions. We identified 250 regulators of gpdh-1 expression with 221 resulting in reduction or complete suppression. GO term analysis through DAVID, KEGG, and Reactome pathways indicated enriched signaling cascades converged on MAPK activation. Rrt-1 knockdown mediated gpdh-1 synthesis is regulated by many kinases affecting diverse cellular processes, but primarily involving immune system function.
Bowie, Jacob, "Genome-wide RNAi Screen Of Kinase Pathways Regulating rrt-1 Constitutive Cytoprotective Gene Expression" (2020). Master's Theses. 1470.
Dr. Elaine Lee