Structural insights into influenza A virus ribonucleoproteins reveal a processive helical track as transcription mechanism
Structural insights into influenza A virus ribonucleoproteins reveal a processive helical track as transcription mechanism
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DOI：
10.1038/s41564-020-0675-3
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发表时间：
2020-03-09
影响因子：
28.3
通讯作者：
Martin-Benito, Jaime
中科院分区：
文献类型：
--
作者：
Coloma, Rocio;Arranz, Rocio;Martin-Benito, Jaime
在这篇文章中，作者确定了流感病毒在病毒核糖核蛋白（vRNP）中的转录机制。这种进行性螺旋轨道机制是由vRNP的螺旋部分的极端灵活性实现的，这允许聚合酶在基因组上移动，同时结合到RNA两端。流感病毒基因组由八种病毒核糖核蛋白（vRNP）组成，每种病毒核糖核蛋白由一个聚合酶拷贝、一个基因组RNA片段和以双螺旋构象排列的多个核蛋白拷贝组成。vRNP是负责信使RNA合成和基因组复制的大分子机器，即子代vRNP的形成。在这里，我们描述了转录过程的结构基础。我们称之为“进行性螺旋轨道”的机制是基于vRNP的螺旋部分的极端灵活性，其允许两个反平行核蛋白-RNA链之间的滑动运动，从而允许聚合酶在基因组上移动，同时与两个RNA末端结合。因此，我们证明阻断这种运动导致vRNP转录活性的抑制。这种机制也揭示了核蛋白在整个复制过程中维持双螺旋结构以使RNA模板可被聚合酶接近的关键作用。
In this Article, the authors identify the mechanism of influenza virus transcription in viral ribonucleoproteins (vRNPs). This processive helical track mechanism is enabled by the extreme flexibility of the helical part of the vRNP, which allows the polymerase to move over the genome while bound to both RNA ends.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.