Genome Wide Screens Point to Disordered Proteins as Sensors of Osmotic Stress

Abstract

Osmotic changes in the cellular environment occur regularly due to both routine cell cycle events and extracellular environmental stress. Being able to sense and adapt to such changes is vital for cell survival. Understanding which proteins help mediate the response is key to understanding how cellular stress adaptation occurs at the molecular level. Here we report on a genome-wide knockout screen used to detect proteins involved in the response to osmotic stress. A cell viability screen was performed on two pools of cells differentially subjected to osmotic stress. Of the genes promoting cell survival under hyperosmotic stress, nearly 10% had sequences that were predicted to be at least 50% disordered. This makes sense because intrinsically disordered proteins lack a stable tertiary structure and have a high degree of surface area exposed to the intracellular environment, rendering them sensitive to changes in the physical-chemical composition of the intracellular environment. We further find that nearly half of these IDPs are associated with DNA binding, implying their sensitivity and involvement in transcription regulation in response to osmotic stress.