Effect of RNA on morphology and dynamics of membraneless organelles

Abstract

AbstractMembraneless organelles (MLOs) are spatiotemporally regulated structures that concentrate multi-valent proteins or RNA, often in response to stress. The proteins enriched within MLOs are often classified as high-valency “scaffolds” or low valency “clients”, with the former being associated with a phase-separation promoting role. In this study, we employ a minimal model for P-body components, with a defined protein-protein interaction network, to study their phase-separation at biologically realistic low protein concentrations. Without RNA multivalent proteins can assemble into solid-like clusters only in the regime of high concentration and stable interactions. RNA molecules promote cluster formation in an RNA-length dependent manner, even in the regime of weak interactions and low protein volume fraction. Our simulations reveal that long RNA chains act as super-scaffolds that stabilize large RNA-protein clusters by recruiting low-valency proteins within them while also ensuring functional “liquid-like” turnover of components. Our results suggest that RNA-mediated phase separation could be a plausible mechanism for spatiotemporally regulated phase-separation in the cell.