Abstract:

Membraneless organelles (MLOs) are spatiotemporally regulated structures that concentrate multivalent 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 superscaffolds 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.

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