Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Japan.
EMBO J. 2021 Jun 15;40(12):e107270. doi: 10.15252/embj.2020107270. Epub 2021 Apr 22.
Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid-liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding biomolecular condensates with optimal sizes and structures in cells.
核仁小体是由 NEAT1_2 结构长链非编码 RNA 构成的。它们的圆柱形特征，具有高度有序的内部组织，使它们有别于典型的液-液相分离凝聚物。我们通过实验和理论研究了核仁小体的形状和组织是如何确定的。我们确定了负责 NEAT1_2 末端壳层定位的 NEAT1_2 RNA 结构域，这决定了其特征内部组织。然后，我们使用软物质物理学，应用了一个理论框架来理解决定 NEAT1_2 组织以及核仁小体的形状、数量和大小的原则。通过将核仁小体视为两亲性嵌段共聚物胶束，我们可以解释和预测在 NEAT1_2 结构域缺失或转录调节时观察到的核仁小体的实验行为。因此，我们提出核仁小体是通过一种微相分离（胶束化）组装而成的嵌段共聚物胶束。这项工作为核蛋白复合物 (RNP) 可以作为嵌段共聚物形成具有最佳大小和结构的 RNA 支架生物分子凝聚物的概念提供了一个基于实验的理论框架。
