PKA regulates stress granule maturation to allow timely recovery after prolonged starvation
Ontology highlight
ABSTRACT: Cells have evolved multiple strategies to survive environmental stress conditions. This includes the formation of membrane-less cytoplasmic ribonucleoprotein structures called stress granules that sequester and protect mRNAs encoding many housekeeping genes. Stress granules are not static biomolecular condensates but transform into solid states during a maturation phase. The deposition of stress granule proteins in solid-like, insoluble aggregates is a hallmark of many neurodegenerative pathologies, thus studies to uncover the pathological link and mechanism underlying the stress granule maturation process are important. In this study we show that yeast stress granules mature into a solid-like state during long-term stationary phase stress, which delays stress granule disassembly and cell cycle restart. Profiling of phosphorylation sites during stationary phase revealed that stress granule maturation is driven by protein kinase A dependent phosphorylation of the stress granule proteome. Indeed, upon stationary phase the catalytic PKA subunits condense in stress granules, where stress granule-localized PKA kinase activity is maintained, whereas in parallel cytoplasmic-localized PKA activity is inhibited. PKA phosphorylates key stress granule components, including the pyruvate kinase Cdc19. Cdc19 phosphorylation by stress granule localized PKA is necessary and sufficient for its maturation in stress granules, where Cdc19 assembles into amyloid-like structures. Importantly, inhibiting PKA during long-term stationary phase prevents stress granule maturation, delaying ordered re-start of cell growth after re-feeding. Taken together, these results describe a stress granule maturation mechanism selectively activated during chronic stress that preserves stress granules integrity and promotes cell survival.
INSTRUMENT(S): Liquid Chromatography MS - negative - HILIC
PROVIDER: MTBLS13923 | MetaboLights | 2026-06-16
REPOSITORIES: MetaboLights
ACCESS DATA
