Different Material States of Pub1 Condensates Define Distinct Modes of Stress Adaptation and Recovery

Abstract

Summary: How cells adapt to varying environmental conditions is largely unknown. Here, we show that, in budding yeast, the RNA-binding and stress granule protein Pub1 has an intrinsic property to form condensates upon starvation or heat stress and that condensate formation is associated with cell-cycle arrest. Release from arrest coincides with condensate dissolution, which takes minutes (starvation) or hours (heat shock). In vitro reconstitution reveals that the different dissolution rates of starvation- and heat-induced condensates are due to their different material properties: starvation-induced Pub1 condensates form by liquid-liquid demixing and subsequently convert into reversible gel-like particles; heat-induced condensates are more solid-like and require chaperones for disaggregation. Our data suggest that different physiological stresses, as well as stress durations and intensities, induce condensates with distinct physical properties and thereby define different modes of stress adaptation and rates of recovery. : Kroschwald et al. show that different environmental stresses induce Pub1 stress granule condensates with different material properties. The material properties define the rate of stress granule dissolution and the requirement for disaggregases. The stress granule constituents are released before reentry into the cell cycle. Keywords: phase separation, condensate, phase transition, stress granule, stress response, molecular chaperone, Hsp104, protein aggregation, cytosolic pH