Paraspeckles are constructed as block copolymer micelles
Paraspeckles are constructed as block copolymer micelles
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DOI：
10.15252/embj.2020107270
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Tomohiro Yamazaki;Tetsuya Yamamoto;Hyura Yoshino;S. Souquere;S. Nakagawa;G. Pierron;T. Hirose
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文献类型：
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作者：
Tomohiro Yamazaki;Tetsuya Yamamoto;Hyura Yoshino;S. Souquere;S. Nakagawa;G. Pierron;T. Hirose
Paraspeckles由NEAT1_2结构长非编码RNA构建。它们特有的圆柱形形状，具有高度有序的内部组织，将它们与典型的液-液相分离的冷凝物区分开来。我们从实验和理论上研究了如何确定paraspeckles的形状和组织。我们确定了NEAT1_2 RNA结构域负责NEAT1_2末端的壳定位，这决定了特征性的内部组织。使用软物质物理学，我们然后应用一个理论框架来理解确定NEAT 1_2组织以及paraspeckles的形状，数量和大小的原则。通过将paraspeckles视为两亲性嵌段共聚物胶束，我们可以解释和预测实验观察到的paraspeckles在NEAT1_2结构域缺失或转录调节后的行为。因此，我们提出paraspeckles是嵌段共聚物胶束组装通过一种类型的微相分离，胶束化。这项工作为核糖核蛋白复合物（RNP）可以作为嵌段共聚物在细胞中形成具有最佳尺寸和结构的RNA支架生物分子缩合物的概念提供了一个基于实验的理论框架。
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.