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Abstract：
Nuclear speckles are nuclear bodies consisting of populations of small and irregularly shaped droplet-like molecular condensates that contain various splicing factors. Recent experiments have revealed the following structural features of nuclear speckles: (I) Each molecular condensate contains SON and SRRM2 proteins, and MALAT1 non-coding RNA surrounds these condensates; (II) During normal interphase of the cell cycle in multicellular organisms, these condensates are broadly distributed throughout the nucleus. In contrast, when cell transcription is suppressed, the condensates fuse and form strongly condensed spherical droplets; (III) SON is dispersed spatially in MALAT1 knocked-down cells and MALAT1 is dispersed in SON knocked-down cells because of the collapse of the nuclear speckles. However, the detailed interactions among the molecules that are mechanistically responsible for the structural variation remain unknown. In this study, a coarse-grained molecular dynamics model of the nuclear speckle was developed by considering the dynamics of SON, SRRM2, MALAT1, and pre-mRNA as representative components of the condensates. The simulations reproduced the structural changes, which were used to predict the interaction network among the representative components of the condensates.
摘要：
核斑点是由含有各种剪接因子的小且不规则形状的液滴状分子缩合物的群体组成的核体。最近的实验揭示了核斑点的以下结构特征：（I）每个分子缩合物含有SON和SRRM2蛋白，和MALAT1非编码RNA围绕这些缩合物；（II）在多细胞生物体细胞周期的正常间期，这些冷凝物广泛分布在整个核中。相比之下,当细胞转录被抑制时，冷凝物融合并形成强烈凝聚的球形液滴；（III）由于核斑点的塌陷，SON在空间上分散在MALAT1敲低的细胞中，而MALAT1分散在SON敲低的细胞中。然而,分子之间的详细相互作用，是机械负责的结构变化仍然未知。在这项研究中,通过考虑SON的动力学，建立了核斑点的粗粒度分子动力学模型，SRRM2，MALAT1和pre-mRNA作为缩合物的代表性成分。模拟再现了结构变化，用于预测冷凝物代表性组分之间的相互作用网络。
