Charge-driven condensation of RNA and proteins suggests broad role of phase separation in cytoplasmic environments.
Charge-driven condensation of RNA and proteins suggests broad role of phase separation in cytoplasmic environments.
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作者：
Dutagaci B;Nawrocki G;Goodluck J;Ashkarran AA;Hoogstraten CG;Lapidus LJ;Feig M
相分离过程越来越被认为是细胞环境中生物大分子的重要组织机制。公认的相分离的驱动因素是多价态和本征无序。在这里，我们证明了球状大分子可以简单地基于静电互补而凝聚。更具体地说，RNA和正电荷蛋白质混合物的相分离是通过结合显微镜和光谱实验的多尺度计算机模拟来描述的。在实验中绘制了相图作为分子浓度的函数，并通过模拟绘制了分子尺寸和温度的函数。由此产生的凝析油被发现至少保留了一定程度的内部动力学，随着分子组成的变化而变化。这些结果提出了一种更一般的相分离原理，它主要基于静电互补，而不像大多数以前的研究那样引用聚合物的性质。模拟结果进一步表明，在异质细胞环境中，核酸和蛋白质组分之间可能会广泛发生这种相分离。
Phase separation processes are increasingly being recognized as important organizing mechanisms of biological macromolecules in cellular environments. Well-established drivers of phase separation are multi-valency and intrinsic disorder. Here, we show that globular macromolecules may condense simply based on electrostatic complementarity. More specifically, phase separation of mixtures between RNA and positively charged proteins is described from a combination of multiscale computer simulations with microscopy and spectroscopy experiments. Phase diagrams were mapped out as a function of molecular concentrations in experiment and as a function of molecular size and temperature via simulations. The resulting condensates were found to retain at least some degree of internal dynamics varying as a function of the molecular composition. The results suggest a more general principle for phase separation that is based primarily on electrostatic complementarity without invoking polymer properties as in most previous studies. Simulation results furthermore suggest that such phase separation may occur widely in heterogenous cellular environment between nucleic acid and protein components.