The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that a centrally located 40 amino acid intrinsically disordered domain drives phase separation of N protein when bound to RNA, with the morphology of the resulting condensates affected by inclusion in the RNA of the putative SARS-CoV-2 packaging signal. The SARS-CoV-2 M protein, normally embedded in the virion membrane with its C-terminus extending into the virion core, independently induces N protein phase separation that is dependent on the N protein's C-terminal dimerization domain and disordered region. Three-component mixtures of N+M+RNA form condensates with mutually exclusive compartments containing N+M or N+RNA, including spherical annular structures in which the M protein coats the outside of an N+RNA condensate. These findings support a model in which phase separation of the N protein with both the viral genomic RNA and the SARS-CoV-2 M protein facilitates RNA packaging and virion assembly.

中文翻译：

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SARS-CoV-2核蛋白磷酸蛋白与RNA和膜相关M蛋白形成互斥的缩合物。

SARS-CoV-2中的多功能核衣壳（N）蛋白与〜30 kb病毒RNA基因组结合，以帮助将其包装到80-90 nm的膜包裹病毒体中。N蛋白由​​N末端RNA结合和C末端二聚化结构域组成，两个结构域侧接三个内在无序的区域。在这里，我们证明了居中位置的40个氨基酸固有无序域在与RNA结合时会驱动N蛋白的相分离，最终的缩合物的形态会受到假定的SARS-CoV-2包装信号包含在RNA中的影响。SARS-CoV-2 M蛋白通常以其C端延伸到病毒体核心的方式嵌入病毒颗粒膜中，独立诱导N蛋白相分离，该分离取决于N蛋白的C端二聚化结构域和无序区域。N + M + RNA的三组分混合物与含有N + M或N + RNA的互斥隔室形成冷凝物，包括球形环状结构，其中M蛋白覆盖N + RNA冷凝物的外部。这些发现支持了一种模型，其中N蛋白与病毒基因组RNA和SARS-CoV-2 M蛋白的相分离促进了RNA包装和病毒体组装。