Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois.
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Wiley Interdiscip Rev RNA. 2019 Mar;10(2):e1514. doi: 10.1002/wrna.1514. Epub 2018 Oct 25.
Cells are segregated into two distinct compartment groups to optimize cellular function. The first is characterized by lipid membranes that encapsulate specific regions and regulate macromolecular flux. The second, known collectively as membraneless organelles (MLOs), lacks defining lipid membranes and exhibits self-organizing properties. MLOs are enriched with specific RNAs and proteins that catalyze essential cellular processes. A prominent sub-class of MLOs are known as nuclear bodies, which includes nucleoli, paraspeckles, and other droplets. These microenvironments contain specific RNAs, exhibit archetypal liquid-liquid phase separation characteristics, and harbor intrinsically disordered, multivalent hub proteins. We present an analysis of nuclear body protein disorder that suggests MLO proteomes are significantly more disordered than structured cellular features. We also outline common MLO ultrastructural features, exemplified by the three sub-compartments present inside the nucleolus. A core-shell configuration, or phase within a phase, is displayed by several nuclear bodies and may be functionally important. Finally, we summarize evidence indicating extensive RNA and protein sharing between distinct nuclear bodies, suggesting functional cooperation and similar nucleation principles. Considering the substantial accumulation of specific coding and noncoding RNA classes inside MLOs, evidence that RNA buffers specific phase transition events, and the absence of a clear correlation between total intrinsic protein disorder and MLO accumulation, we conclude that RNA biogenesis may play a key role in MLO formation, internal organization, and function. This article is categorized under: RNA Export and Localization > RNA Localization RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
细胞被分隔成两个不同的区室群，以优化细胞功能。第一个区室群的特征是脂质膜，它包裹着特定的区域并调节大分子的流动。第二个区室群被统称为无膜细胞器（MLO），缺乏定义明确的脂质膜，表现出自组织特性。MLO 富含特定的 RNA 和蛋白质，这些 RNA 和蛋白质催化着重要的细胞过程。MLO 的一个突出的亚类是核体，包括核仁、核小体和其他液滴。这些微环境包含特定的 RNA，表现出典型的液-液相分离特征，并含有固有无序、多价中心蛋白。我们对核体蛋白无序性进行了分析，表明 MLO 蛋白质组比结构细胞特征显著更无序。我们还概述了常见的 MLO 超微结构特征，以核仁内存在的三个亚区室为例。核心-壳结构，或相中的相，被几种核体显示出来，这可能具有功能重要性。最后，我们总结了表明不同核体之间存在广泛的 RNA 和蛋白质共享的证据，这表明存在功能合作和相似的成核原则。考虑到大量特定编码和非编码 RNA 类在 MLO 内的积累，以及 RNA 缓冲特定相变事件的证据，以及总内在蛋白无序性与 MLO 积累之间没有明显的相关性，我们得出结论，RNA 生物发生可能在 MLO 的形成、内部组织和功能中发挥关键作用。本文属于以下分类：RNA 输出和定位 > RNA 定位 RNA 与蛋白质和其他分子的相互作用 > 蛋白-RNA 相互作用：功能意义。
