Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
Nat Microbiol. 2020 May;5(5):727-734. doi: 10.1038/s41564-020-0675-3. Epub 2020 Mar 9.
The influenza virus genome consists of eight viral ribonucleoproteins (vRNPs), each consisting of a copy of the polymerase, one of the genomic RNA segments and multiple copies of the nucleoprotein arranged in a double helical conformation. vRNPs are macromolecular machines responsible for messenger RNA synthesis and genome replication, that is, the formation of progeny vRNPs. Here, we describe the structural basis of the transcription process. The mechanism, which we call the 'processive helical track', is based on the extreme flexibility of the helical part of the vRNP that permits a sliding movement between both antiparallel nucleoprotein-RNA strands, thereby allowing the polymerase to move over the genome while bound to both RNA ends. Accordingly, we demonstrate that blocking this movement leads to inhibition of vRNP transcriptional activity. This mechanism also reveals a critical role of the nucleoprotein in maintaining the double helical structure throughout the copying process to make the RNA template accessible to the polymerase.
流感病毒基因组由八个病毒核糖核蛋白（vRNP）组成，每个 vRNP 由一个聚合酶、一个基因组 RNA 片段和多个排列成双螺旋构象的核蛋白组成。vRNP 是负责信使 RNA 合成和基因组复制的大分子机器，即形成子代 vRNP。在这里，我们描述了转录过程的结构基础。我们称之为“连续螺旋轨道”的机制基于 vRNP 螺旋部分的极端灵活性，允许在两条反平行的核蛋白-RNA 链之间发生滑动运动，从而使聚合酶在与两个 RNA 末端结合的同时在基因组上移动。因此，我们证明阻止这种运动可导致 vRNP 转录活性的抑制。该机制还揭示了核蛋白在整个复制过程中维持双链结构的关键作用，以使 RNA 模板可被聚合酶访问。
