Leiden Institute of Chemistry, Leiden University, RA, Leiden, The Netherlands.
Friedrich-Loeffler-Institut, Institute of Diagnostic Virology, Greifswald, Germany.
RNA Biol. 2021 Dec;18(12):2321-2329. doi: 10.1080/15476286.2021.1907044. Epub 2021 Apr 16.
After infection by flaviviruses like Zika and West Nile virus, eukaryotic hosts employ the well-conserved endoribonuclease Xrn1 to degrade the viral genomic RNA. Within the 3' untranslated regions, this enzyme encounters intricate Xrn1-resistant structures. This results in the accumulation of subgenomic flaviviral RNAs, an event that improves viral growth and aggravates viral pathogenicity. Xrn1-resistant RNAs have been established throughout the flaviviral genus, but not yet throughout the entire family. In this work, we use previously determined characteristics of these structures to identify homologous sequences in many members of the genera pegivirus, hepacivirus and pestivirus. We used structural alignment and mutational analyses to establish that these sequences indeed represent Xrn1-resistant RNA and that they employ the general features of the flaviviral xrRNAs, consisting of a double pseudoknot formed by five base-paired regions stitched together by a crucial triple base interaction. Furthermore, we demonstrate that the pestivirus Bungowannah virus produces subgenomic RNA . Altogether, these results indicate that viruses make use of a universal Xrn1-resistant RNA throughout the family.
在感染黄病毒（如寨卡病毒和西尼罗河病毒）后，真核宿主利用高度保守的内切核糖核酸酶 Xrn1 降解病毒基因组 RNA。在 3'非翻译区，该酶遇到复杂的 Xrn1 抗性结构。这导致亚基因组 flaviviral RNA 的积累，这一事件改善了病毒的生长并加重了病毒的致病性。Xrn1 抗性 RNA 已在整个黄病毒属中得到确立，但尚未在整个家族中得到确立。在这项工作中，我们使用这些结构的先前确定的特征来鉴定属 pegivirus、hepacivirus 和 pestivirus 中许多成员的同源序列。我们使用结构比对和突变分析来确定这些序列确实代表 Xrn1 抗性 RNA，并且它们采用 flaviviral xrRNAs 的一般特征，由由通过关键的三碱基相互作用缝合在一起的五个碱基配对区域形成的双链假结组成。此外，我们证明了瘟病毒 Bungowannah 病毒产生亚基因组 RNA。总之，这些结果表明病毒在整个家族中利用通用的 Xrn1 抗性 RNA。
