Dicer-2 processes diverse viral RNA species.
Dicer-2 processes diverse viral RNA species.
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DOI：
10.1371/journal.pone.0055458
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cherry S
中科院分区：
文献类型：
--
作者：
Sabin LR;Zheng Q;Thekkat P;Yang J;Hannon GJ;Gregory BD;Tudor M;Cherry S
RNA沉默途径在基因调控、病毒感染和转座子控制中起着关键作用。RNA干扰（RNAi）是由小干扰RNA（siRNA）介导的，其通过Dicer从双链（ds）RNA前体释放并引导RNA诱导的沉默复合物（RISC）靶向。尽管已经发现了将小RNA分选到RISC中的原理，但对Dicer蛋白可以靶向的RNA种类的谱，特别是感染期间存在的病毒RNA，知之甚少。Dicer-2通过从病毒RNA产生病毒衍生的siRNA来有效地限制昆虫中的病毒感染。为了更好地表征Dicer-2的底物，我们使用高通量测序检测了在果蝇抗病毒RNAi响应四种不同病毒期间产生的病毒衍生的siRNA。我们发现每种病毒都是RNAi途径的独特靶向;切割底物包括dsRNA复制中间体和分子内RNA茎环。例如，由裂谷热病毒编码的推定的基因间RNA发夹在果蝇和蚊子细胞中都产生丰富的小RNA，而在果蝇中产生丰富的小RNA的牛痘病毒基因组末端内的重复序列被发现在昆虫和哺乳动物细胞中都转录。此外，我们提供的证据表明，Dicer-2靶向的RNA种类可以通过RNAi的病毒抑制因子的存在来调节。这项研究揭示了病毒基因组中几个新的、高度靶向的特征，为病毒复制、病毒免疫逃避策略和抗病毒RNAi机制提供了深入了解。
RNA silencing pathways play critical roles in gene regulation, virus infection, and transposon control. RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets. Although principles governing small RNA sorting into RISC have been uncovered, the spectrum of RNA species that can be targeted by Dicer proteins, particularly the viral RNAs present during an infection, are poorly understood. Dicer-2 potently restricts viral infection in insects by generating virus-derived siRNAs from viral RNA. To better characterize the substrates of Dicer-2, we examined the virus-derived siRNAs produced during the Drosophila antiviral RNAi response to four different viruses using high-throughput sequencing. We found that each virus was uniquely targeted by the RNAi pathway; dicing substrates included dsRNA replication intermediates and intramolecular RNA stem loops. For instance, a putative intergenic RNA hairpin encoded by Rift Valley Fever virus generates abundant small RNAs in both Drosophila and mosquito cells, while repetitive sequences within the genomic termini of Vaccinia virus, which give rise to abundant small RNAs in Drosophila, were found to be transcribed in both insect and mammalian cells. Moreover, we provide evidence that the RNA species targeted by Dicer-2 can be modulated by the presence of a viral suppressor of RNAi. This study uncovered several novel, heavily targeted features within viral genomes, offering insight into viral replication, viral immune evasion strategies, and the mechanism of antiviral RNAi.
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影响因子：
4.2
作者：
Campbell CL;Keene KM;Brackney DE;Olson KE;Blair CD;Wilusz J;Foy BD
通讯作者：
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影响因子：
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作者：
ALEXANDER, WA;MOSS, B;FUERST, TR
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DOI：
10.1073/pnas.0813412106
发表时间：
2009-03-31
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影响因子：
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通讯作者：
Cullen, Bryan R.