RNase L-induced bodies sequester subgenomic flavivirus RNAs and re-establish host RNA decay.
RNase L-induced bodies sequester subgenomic flavivirus RNAs and re-establish host RNA decay.
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RNase L 诱导的体隔离亚基因组黄病毒 RNA 并重新建立宿主 RNA 衰变。
DOI：
10.1101/2024.03.25.586660
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Burke,JamesM
中科院分区：
文献类型：
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作者：
Watkins,JMonty;Burke,JamesM
亚基因组黄病毒RNA（sfRNA）是在黄病毒的3 '-UTR中编码的结构化RNA元件，其通过抑制细胞RNA衰变机制来促进病毒感染。在此，我们使用单分子RNA荧光原位杂交（smRNA-FISH）和超分辨率显微镜分析了西尼罗河病毒，寨卡病毒或登革热病毒血清型2感染期间sfRNA的产生。我们表明，sfRNA最初弥漫定位在胞质溶胶或加工机构（P-机构）。然而，在宿主抗病毒核糖核酸内切酶（核糖核酸酶L（RNase L））活化后，几乎所有sfRNA重新定位于称为RNase L诱导体（RLB）的抗病毒生物缩合物。RLB介导的sfRNA隔离减少了sfRNA与P体中RNA衰变机制的结合，这与增加的病毒RNA衰变一致。这些发现确立了RLB在促进病毒RNA衰变中的作用，证明了RNA衰变和生物浓缩水平上的复杂宿主-病原体相互作用。
Subgenomic flavivirus RNAs (sfRNAs) are structured RNA elements encoded in the 3’-UTR of flaviviruses that promote viral infection by inhibiting cellular RNA decay machinery. Herein, we analyze the production of sfRNAs using single-molecule RNA fluorescence in situ hybridization (smRNA-FISH) and super-resolution microscopy during West Nile virus, Zika virus, or Dengue virus serotype 2 infection. We show that sfRNAs are initially localized diffusely in the cytosol or in processing bodies (P-bodies). However, upon activation of the host antiviral endoribonuclease, Ribonuclease L (RNase L), nearly all sfRNAs re-localize to antiviral biological condensates known as RNase L-induced bodies (RLBs). RLB-mediated sequestration of sfRNAs reduces sfRNA association with RNA decay machinery in P-bodies, which coincides with increased viral RNA decay. These findings establish a role of RLBs in promoting viral RNA decay, demonstrating the complex host-pathogen interactions at the level of RNA decay and biological condensation.