Structural analysis of 3'UTRs in insect flaviviruses reveals novel determinants of sfRNA biogenesis and provides new insights into flavivirus evolution.
Structural analysis of 3'UTRs in insect flaviviruses reveals novel determinants of sfRNA biogenesis and provides new insights into flavivirus evolution.
复制标题
DOI：
10.1038/s41467-022-28977-3
复制
发表时间：
2022-03-11
影响因子：
16.6
通讯作者：
Khromykh AA
中科院分区：
文献类型：
--
作者：
Slonchak A;Parry R;Pullinger B;Sng JDJ;Wang X;Buck TF;Torres FJ;Harrison JJ;Colmant AMG;Hobson-Peters J;Hall RA;Tuplin A;Khromykh AA
亚基因组黄病毒RNA（sfRNA）是由致病性蚊媒黄病毒（MBF）产生的病毒源性非编码RNA，用于对抗宿主的抗病毒反应。迄今为止，非致病性黄病毒产生和利用sfRNA的能力在很大程度上仍未被探索，并且不清楚XRN1抗性在黄病毒进化和宿主适应中起什么作用。本文显示了由仅在蚊子中复制的几种昆虫特异性黄病毒（ISF）产生的sfRNA，并确定了其完整3'UTR的二级结构。还鉴定了负责ISF sfRNA生物发生的xrRNA，并证明了这些sfRNA在病毒复制中的作用。我们证明了所有经典ISF的3'UTR，除了按蚊属相关病毒，和双宿主相关ISF Binjari病毒含有重复的xrRNA。我们还揭示了新的结构元件在3'UTR的双重主机相关和Anopories相关的经典ISFs。基于结构的系统发育分析表明，在按蚊种相关ISF中鉴定的xrRNA可能是ISF和MBF的xrRNA的祖先。此外，我们的数据提供了证据，证明在黄病毒的进化中选择了重复的xrRNA以提供功能冗余，如果其中一种结构因突变或错误折叠而失效，则保留了sfRNA的产生。亚基因组黄病毒RNA（sfRNA）由致病性黄病毒产生以抵消宿主的抗病毒应答。sfRNA是宿主核糖核酸外切酶XRN1对病毒RNA不完全降解的产物，其在3个UTR中的XRN1抗性结构元件（xrRNA）上停滞。在这里，Slonchak等人鉴定了蚊子特异性黄病毒的xrRNA，表征了它们阻止XRN1和产生sfRNA的能力，并应用基于结构的系统发育分析为这些元件的进化选择提供证据。
Subgenomic flaviviral RNAs (sfRNAs) are virus-derived noncoding RNAs produced by pathogenic mosquito-borne flaviviruses (MBF) to counteract the host antiviral response. To date, the ability of non-pathogenic flaviviruses to produce and utilise sfRNAs remains largely unexplored, and it is unclear what role XRN1 resistance plays in flavivirus evolution and host adaptation. Herein the production of sfRNAs by several insect-specific flaviviruses (ISFs) that replicate exclusively in mosquitoes is shown, and the secondary structures of their complete 3’UTRs are determined. The xrRNAs responsible for the biogenesis of ISF sfRNAs are also identified, and the role of these sfRNAs in virus replication is demonstrated. We demonstrate that 3’UTRs of all classical ISFs, except Anopheles spp-asscoaited viruses, and of the dual-host associated ISF Binjari virus contain duplicated xrRNAs. We also reveal novel structural elements in the 3’UTRs of dual host-associated and Anopheles-associated classical ISFs. Structure-based phylogenetic analysis demonstrates that xrRNAs identified in Anopheles spp-associated ISF are likely ancestral to xrRNAs of ISFs and MBFs. In addition, our data provide evidence that duplicated xrRNAs are selected in the evolution of flaviviruses to provide functional redundancy, which preserves the production of sfRNAs if one of the structures is disabled by mutations or misfolding. Subgenomic flaviviral RNAs (sfRNAs) are produced by pathogenic flaviviruses to counteract the host antiviral response. sfRNAs are products of incomplete degradation of viral RNA by the host exoribonuclease XRN1 which stalls on XRN1-resistant structural elements (xrRNAs) in the 3‟UTR. Here, Slonchak et al. identify xrRNAs for mosquito-specific flaviviruses, characterize their ability to stall XRN1 and produce sfRNAs, and apply structure-based phylogenetic analysis to provide evidence for evolutionary selection of these elements.
登录
查看更多内容
影响因子：
3
作者：
Katoh K;Toh H
通讯作者：
Toh H
影响因子：
4.5
作者：
Karabiber, Fethullah;McGinnis, Jennifer L.;Weeks, Kevin M.
通讯作者：
Weeks, Kevin M.
影响因子：
5.4
作者：
Goertz, G. P.;Fros, J. J.;Pijlman, G. P.
通讯作者：
Pijlman, G. P.
DOI：
10.1261/rna.077065.120
发表时间：
2021-01
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Jones RA;Steckelberg AL;Vicens Q;Szucs MJ;Akiyama BM;Kieft JS
通讯作者：
Kieft JS
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM