Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
J Phys Chem B. 2021 May 20;125(19):5035-5044. doi: 10.1021/acs.jpcb.1c02286. Epub 2021 May 10.
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.
无膜细胞器 (MLOs) 是时空调节结构，可浓缩多价蛋白质或 RNA，通常是对压力的响应。富含 MLO 的蛋白质通常被分类为高价“支架”或低价“客户”，前者与相分离促进作用有关。在这项研究中，我们采用了一个具有明确定义的蛋白质-蛋白质相互作用网络的 P 体成分的最小模型，来研究它们在具有生物学意义的低蛋白浓度下的相分离。没有 RNA，多价蛋白质只能在高浓度和稳定相互作用的情况下组装成固态样簇。RNA 分子以 RNA 长度依赖的方式促进簇的形成，即使在弱相互作用和低蛋白体积分数的情况下也是如此。我们的模拟结果表明，长 RNA 链充当超支架，通过在其中招募低价蛋白质来稳定大的 RNA-蛋白质簇，同时确保组件的功能性“液体样”周转。我们的结果表明，RNA 介导的相分离可能是细胞中时空调节相分离的一种合理机制。
