RNase III nucleases from diverse kingdoms serve as antiviral effectors.

RNase III nucleases from diverse kingdoms serve as antiviral effectors.
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DOI:
10.1038/nature22990
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发表时间:
2017-07-06
期刊:
影响因子:
64.8
通讯作者:
tenOever BR
tenOever BR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Aguado LC;Schmid S;May J;Sabin LR;Panis M;Blanco-Melo D;Shim JV;Sachs D;Cherry S;Simon AE;Levraud JP;tenOever BR

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与原核生物中基于dna的病毒相比,真核生物的出现为RNA病毒的繁殖提供了必要的区隔化和膜环境,从而产生了对RNA靶向抗病毒系统的需求。目前,真核生物至少采用两种主要的防御策略,即抗病毒RNA干扰(RNAi)和干扰素(IFN)系统。在这里,我们证明了来自生命所有三个结构域的Drosha和相关的RNase III核糖核酸酶也能引发rna靶向抗病毒活性。配体在这类蛋白质上的指数富集(SELEX)系统进化说明了对未支链RNA干环的识别。生化分析表明,在这种情况下,Drosha可作为抗病毒钳,对多种正链RNA病毒的RNA依赖RNA聚合酶(RdRps)施加位阻。我们提出了多种真核生物(包括植物、节肢动物、无脊椎脊索动物和鱼类)响应病毒的RNase III核酸酶细胞质易位的证据。这些数据表明RNase III对病毒RNA的识别是一种独立的抗病毒防御,可能早于其他已知的真核抗病毒系统。
In contrast to the DNA-based viruses in prokaryotes, the emergence of eukaryotes provided the necessary compartmentalization and membranous environment for RNA viruses to flourish, creating the need for an RNA-targeting antiviral system. Present day eukaryotes employ at least two main defense strategies that emerged as a result of this viral shift, namely antiviral RNA interference (RNAi) and the interferon (IFN) system. Here, we demonstrate that Drosha and related RNase III ribonucleases from all three domains of life, also elicit RNA-targeting antiviral activity. Systemic evolution of ligands by exponential enrichment (SELEX) on this class of proteins illustrates the recognition of unbranched RNA stem loops. Biochemical analyses reveal that in this context, Drosha functions as an antiviral clamp, conferring steric hindrance on the RNA dependent RNA polymerases (RdRps) of diverse positive stranded RNA viruses. We present evidence for cytoplasmic translocation of RNase III nucleases in response to virus in diverse eukaryotes including: plants, arthropods, invertebrate chordates, and fish. These data implicate RNase III recognition of viral RNA as an antiviral defense that is independent of, and possibly predates, other known eukaryotic antiviral systems.
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发表时间: 2014-05-13
影响因子: 11.1
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