Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly.

Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly.
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DOI:
10.1016/j.celrep.2018.01.036
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发表时间:
2018-02-06
期刊:
影响因子:
8.8
通讯作者:
Parker R
Parker R
中科院分区:
生物学1区
文献类型:
--
作者:
Protter DSW;Rao BS;Van Treeck B;Lin Y;Mizoue L;Rosen MK;Parker R

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真核细胞含有大的RNA-蛋白质组装体,称为RNP颗粒,其组装由传统的蛋白质相互作用和内在无序的蛋白质结构域促进。使用RNP颗粒作为一个例子,我们提供了证据的组装机制的大细胞结构,其中特定的蛋白质-蛋白质或蛋白质-RNA相互作用与混杂的相互作用的内在无序区域(IDR)。这种协同组装机制阐明了RNP颗粒组装,并解释了为什么RNP颗粒的许多组分和其他大型动态组装体含有与特定蛋白质-蛋白质或蛋白质-RNA相互作用模块连接的IDR。我们建议组装基于特定的相互作用和混杂的IDR的组合是真核细胞的共同特征。许多RNA结合蛋白含有无序区域。Protter等人发现这些区域与其他蛋白质非特异性相互作用,这可以破坏体外相分离。他们还发现,混杂的相互作用与特定的相互作用协同作用,以促进相分离和形成更高阶的结构,如RNP颗粒。
Eukaryotic cells contain large RNA-protein assemblies referred to as RNP granules, whose assembly is promoted by both traditional protein interactions and intrinsically disordered protein domains. Using RNP granules as an example, we provide evidence for an assembly mechanism of large cellular structures wherein specific protein-protein or protein-RNA interactions act together with promiscuous interactions of intrinsically disordered regions (IDRs). This synergistic assembly mechanism illuminates RNP granule assembly and explains why many components of RNP granules, and other large dynamic assemblies, contain IDRs linked to specific protein-protein or protein-RNA interaction modules. We suggest assemblies based on combinations of specific interactions and promiscuous IDRs are common features of eukaryotic cells. Many RNA-binding proteins contain disordered regions. Protter et al. find that these regions interact nonspecifically with other proteins, which can disrupt phase separation in vitro. They also find that promiscuous interactions synergize with specific interactions to promote phase separation and formation of higher-order structures, like RNP granules.
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