Partial demixing of RNA-protein complexes leads to intradroplet patterning in phase-separated biological condensates

Partial demixing of RNA-protein complexes leads to intradroplet patterning in phase-separated biological condensates
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DOI:
10.1103/physreve.99.012411
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发表时间:
2019-01-10
期刊:
影响因子:
2.4
通讯作者:
Newby, Jay
Newby, Jay
中科院分区:
物理与天体物理3区
文献类型:
--
作者:
Gasior, Kelsey;Zhao, Jia;Newby, Jay

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细胞内组织的一种新兴机制是液-液相分离(LLPS)。在细胞核和细胞质中都可以发现,液体状的液滴凝结成隔间,被认为可以促进和抑制特定的生物化学反应。在这项工作中,一个多相的,Cahn-Hilliard扩散界面模型被用来研究RNA-蛋白质相互作用驱动LLPS。我们创建了一个二价系统,允许两种不同种类的蛋白质-RNA复合物和模型的竞争,出现了一个共享的结合伙伴,游离蛋白质。有了这个系统,我们证明了不同的RNA-蛋白质复合物的结合和解结合导致不同的空间模式的形成和液滴内的动力学。空间模式的初始形成和瞬时行为都受到RNA-蛋白质复合物之间游离蛋白质交换的影响。这项研究表明,时空异质性可以出现在相分离的生物凝聚体与简单的结合反应和竞争。液滴内图案化可以影响液滴组成,并且随后影响更大尺度上的细胞组织。
An emerging mechanism for intracellular organization is liquid-liquid phase separation (LLPS). Found in both the nucleus and the cytoplasm, liquidlike droplets condense to create compartments that are thought to promote and inhibit specific biochemistry. In this work, a multiphase, Cahn-Hilliard diffuse interface model is used to examine RNA-protein interactions driving LLPS. We create a bivalent system that allows for two different species of protein-RNA complexes and model the competition that arises for a shared binding partner, free protein. With this system we demonstrate that the binding and unbinding of distinct RNA-protein complexes leads to diverse spatial pattern formation and dynamics within droplets. Both the initial formation and transient behavior of spatial patterning are subject to the exchange of free proteins between RNA-protein complexes. This study illustrates that spatiotemporal heterogeneity can emerge within phase-separated biological condensates with simple binding reactions and competition. Intradroplet patterning may influence droplet composition and, subsequently, cellular organization on a larger scale.