研究發現dsRNA病毒中多個核苷酸液態晶體幾何結構
作者：
小柯機器人發布時間：2019/7/18 16:29:21
牛津大學Juha T. Huiskonen團隊取得一項新突破。他們提出了dsRNA病毒中多個高度濃縮的核苷酸液態晶體幾何結構。該研究於2019年5月29日發表於國際學術期刊《自然》雜誌上。
通過冷凍電鏡解析囊狀噬菌體科的dsRNA基因組結構，發現其dsRNA可採取類似dsDNA基因組的單個捲軸結構。課題組發現在這組病毒中，依賴RNA的RNA聚合酶不直接對基因組排序，並且dsRNA可以採用多種構象。該課題組建立了一個包含90%基因組的模型，並以此為主題來量化包裝密度的變化，並描述緊密壓縮的核酸所表現出的不同液晶幾何形狀。他們的結果表明，dsDNA包裝的標準模型可以擴展到dsRNA病毒。
據悉，描述成熟病毒粒子的基因組是理解病毒裝配和感染的高度動態過程的關鍵。由於DNA和RNA的細胞命運不同，雙鏈DNA和dsRNA病毒的生命周期也不同。在核酸包裝方面，缺乏基因組分割和衣殼內轉錄機制的dsDNA病毒主題主要表現為單軸基因組組織。由於dsRNA釋放到細胞質中觸發宿主防禦機制，dsRNA病毒將其基因組保留在一個包含RNA複製和轉錄所需酶的核心顆粒中。dsRNA病毒主題的基因組在分割程度上有很大的差異。在呼腸弧病毒屬家族成員中，基因組由10-12個片段組成，並表現出由依賴RNA的RNA聚合酶介導的非線軸排列機制。然而，這種排列是否是dsRNA病毒的一個普遍特徵還不清楚。
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