Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.

ABSTRACT: Protein kinase A (PKA) plays a crucial and conserved role in various biological processes across species. Despite its significance, tissue-level regulatory networks controlling PKA activity remain incompletely characterized. In this study, we develop a live animal PKA sensor that can faithfully indicate changes in PKA activity in the intestines of Caenorhabditis elegans (C. elegans). Using complementary genome-wide and intestine-specific RNAi screens, we reveal both intestine-autonomous and non-autonomous regulators of intestinal PKA. Notably, we show that inhibiting mitochondrial oxidative phosphorylation, either through RNAi or chemical treatment, leads to a marked increase in intestinal PKA activity. Additionally, we demonstrate that the pyrimidine synthesis pathway serves as a critical

SUBMITTER: Li Y 

PROVIDER: S-EPMC12379208 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature