Phosphorylation-mediated RNA/peptide complex coacervation as a model for intracellular liquid organelles
Phosphorylation-mediated RNA/peptide complex coacervation as a model for intracellular liquid organelles
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DOI：
10.1038/nchem.2414
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发表时间：
2016-02-01
期刊：
影响因子：
21.8
通讯作者：
Keating, Christine D.
中科院分区：
文献类型：
--
作者：
Aumiller, William M., Jr.;Keating, Christine D.
生物细胞具有高度的组织性，包含众多亚细胞区室。磷酸化被假定为一种控制类液体的富含RNA和蛋白质的细胞内体（即无膜细胞器）组装/拆卸的手段。在此，我们证明了RNA与阳离子肽的电荷介导的相分离（或复合凝聚）能够产生能够可逆地分隔生物分子的简单模型类液体细胞器。利用一对激酶/磷酸酶，通过改变肽的磷酸化状态来控制这些液体小体的形成和溶解。即使是单个丝氨酸残基的修饰也会引起液滴生成的相变。短阳离子肽和长得多的多聚阴离子RNA之间的静电相互作用驱动了相分离。凝聚物也在二氧化硅珠上形成，这是在特定细胞内位点定位的一个原始模型。这项工作支持复合凝聚的磷酸化调节是无膜细胞器中动态细胞内区室化的一种可行机制。
Biological cells are highly organized, with numerous subcellular compartments. Phosphorylation has been hypothesized as a means to control the assembly/disassembly of liquid-like RNA-and protein-rich intracellular bodies, or liquid organelles, that lack delimiting membranes. Here, we demonstrate that charge-mediated phase separation, or complex coacervation, of RNAs with cationic peptides can generate simple model liquid organelles capable of reversibly compartmentalizing biomolecules. Formation and dissolution of these liquid bodies was controlled by changes in peptide phosphorylation state using a kinase/phosphatase enzyme pair. The droplet-generating phase transition responded to modification of even a single serine residue. Electrostatic interactions between the short cationic peptides and the much longer polyanionic RNAs drove phase separation. Coacervates were also formed on silica beads, a primitive model for localization at specific intracellular sites. This work supports phosphoregulation of complex coacervation as a viable mechanism for dynamic intracellular compartmentalization in membraneless organelles.