牛津大学Juha T. Huiskonen团队取得一项新突破。他们提出了dsRNA病毒中多个高度浓缩的核苷酸液态晶体几何结构。该研究于2019年5月29日发表于国际学术期刊《自然》杂志上。

通过冷冻电镜解析囊状噬菌体科的dsRNA基因组结构，发现其dsRNA可采取类似dsDNA基因组的单个卷轴结构。课题组发现在这组病毒中，依赖RNA的RNA聚合酶不直接对基因组排序，并且dsRNA可以采用多种构象。该课题组建立了一个包含90%基因组的模型，并以此为主题来量化包装密度的变化，并描述紧密压缩的核酸所表现出的不同液晶几何形状。他们的结果表明，dsDNA包装的标准模型可以扩展到dsRNA病毒。

据悉，描述成熟病毒粒子的基因组是理解病毒装配和感染的高度动态过程的关键。由于DNA和RNA的细胞命运不同，双链DNA和dsRNA病毒的生命周期也不同。在核酸包装方面，缺乏基因组分割和衣壳内转录机制的dsDNA病毒主题主要表现为单轴基因组组织。由于dsRNA释放到细胞质中触发宿主防御机制，dsRNA病毒将其基因组保留在一个包含RNA复制和转录所需酶的核心颗粒中。dsRNA病毒主题的基因组在分割程度上有很大的差异。在呼肠弧病毒属家族成员中，基因组由10-12个片段组成，并表现出由依赖RNA的RNA聚合酶介导的非线轴排列机制。然而，这种排列是否是dsRNA病毒的一个普遍特征还不清楚。

附：英文原文

Title: Multiple liquid crystalline geometries of highly compacted nucleic acid in a dsRNA virus

Author: Serban L. Ilca, Xiaoyu Sun, Kamel El Omari, Abhay Kotecha, Felix de Haas, Frank DiMaio, Jonathan M. Grimes, David I. Stuart, Minna M. Poranen, Juha T. Huiskonen

Issue&Volume:Volume 570 Issue 7760, 13 June 2019

Abstract: Characterizing the genome of mature virions is pivotal to understanding the highly dynamic processes of virus assembly and infection. Owing to the different cellular fates of DNA and RNA, the life cycles of double-stranded (ds)DNA and dsRNA viruses are dissimilar. In terms of nucleic acid packing, dsDNA viruses, which lack genome segmentation and intra-capsid transcriptional machinery, predominantly display single-spooled genome organizations. Because the release of dsRNA into the cytoplasm triggers host defence mechanisms9, dsRNA viruses retain their genomes within a core particle that contains the enzymes required for RNA replication and transcription10,11,12. The genomes of dsRNA viruses vary greatly in the degree of segmentation. In members of the Reoviridae family, genomes consist of 10–12 segments and exhibit a non-spooled arrangement mediated by RNA-dependent RNA polymerases11,12,13,14. However, whether this arrangement is a general feature of dsRNA viruses remains unknown. Here, using cryo-electron microscopy to resolve the dsRNA genome structure of the tri-segmented bacteriophage 6 of the Cystoviridae family, we show that dsRNA viruses can adopt a dsDNA-like single-spooled genome organization. We find that in this group of viruses, RNA-dependent RNA polymerases do not direct genome ordering, and the dsRNA can adopt multiple conformations. We build a model that encompasses 90% of the genome, and use this to quantify variation in the packing density and to characterize the different liquid crystalline geometries that are exhibited by the tightly compacted nucleic acid. Our results demonstrate that the canonical model for the packing of dsDNA can be extended to dsRNA viruses.

DOI: https://doi.org/10.1038/s41586-019-1229-9

Source: https://www.nature.com/articles/s41586-019-1229-9