Viral RNA exported from the coronavirus replication organelle is likely to be mediated by a crown-shaped molecular pore. A gateway to the cytosol Coronaviruses transform host cell membranes into peculiar double-membrane vesicles that have long been thought to accommodate viral genome replication. However, because these compartments appeared to be completely sealed, it has remained unknown how the newly made viral RNA could be exported to the cytosol for translation and packaging into new virions. Wolff et al. used cryo–electron microscopy to identify a molecular pore that spans the double membrane (see the Perspective by Unchwaniwala and Ahlquist). Six copies of a large coronavirus transmembrane protein formed the core of this structure, which may constitute a viral RNA export channel and provide a target for future antiviral interventions. Science, this issue p. 1395; see also p. 1306 Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.

中文翻译：

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一个分子孔跨越冠状病毒复制细胞器的双膜

从冠状病毒复制细胞器输出的病毒RNA很可能是由一个冠状分子孔介导的。通往胞质溶胶的途径 冠状病毒将宿主细胞膜转化为特殊的双膜囊泡，长期以来人们认为这种双膜囊泡可容纳病毒基因组复制。然而，由于这些隔室似乎是完全密封的，因此新制造的病毒 RNA 如何被输出到细胞质中以翻译和包装成新的病毒粒子仍然是未知的。沃尔夫等人。使用冷冻电子显微镜来识别跨越双膜的分子孔（参见 Unchwaniwala 和 Ahlquist 的观点）。一个大的冠状病毒跨膜蛋白的六个拷贝构成了该结构的核心，它可能构成病毒RNA输出通道，并为未来的抗病毒干预提供目标。科学，这个问题 p。1395; 另见第 1306 冠状病毒基因组复制与病毒诱导的胞质双膜囊泡有关，这可能为受感染细胞中的病毒 RNA 合成提供量身定制的微环境。然而，目前尚不清楚新合成的基因组和信使 RNA 如何从这些密封的复制隔室传播到细胞质，以确保它们的翻译和子代病毒粒子的组装。在这项研究中，我们使用细胞冷冻电子显微镜来观察分子孔复合物，该复合物跨越双膜囊泡的两个膜，并允许将 RNA 输出到细胞质中。发现大型病毒跨膜蛋白的六聚体组装形成了冠状复合物的核心。