Silencing of Host Genes Directed by Virus-Derived Short Interfering RNAs in Caenorhabditis elegans
Silencing of Host Genes Directed by Virus-Derived Short Interfering RNAs in Caenorhabditis elegans
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DOI：
10.1128/jvi.01501-12
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发表时间：
2012-11-01
影响因子：
5.4
通讯作者：
Lu, Rui
中科院分区：
文献类型：
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作者：
Guo, Xunyang;Li, Wan-Xiang;Lu, Rui
小干扰RNA（siRNA）通过RNase III样酶Dicer从病毒复制中间体加工而成，在真菌、植物和无脊椎动物中引导序列特异性抗病毒沉默。在植物中，病毒衍生的siRNA（viRNA）可以靶向并沉默细胞转录物，并且在某些情况下，负责诱导植物疾病。目前仍不清楚viRNA是否也能够调节动物界中细胞基因的表达，尽管已知动物病毒编码的microRNA（miRNAs）引导宿主基因的有效沉默，从而促进病毒复制。在这份报告中，我们表明，来自修饰的野田村病毒的viRNA触发了线虫线虫中内源基因或转基因产生的同源细胞转录本的有效沉默。与在植物中发现的一样，在C.线虫还涉及RRF-1，一种蠕虫RNA依赖性RNA聚合酶（RdRP），已知其以不依赖于Dicer的方式产生单链二级siRNA。我们进一步证明了C. elegans是可遗传的，这表明VIGS有可能在后代中产生深刻的表观遗传后果。总之，这些发现首次证实了viRNA具有调节动物界宿主基因表达的潜力。最重要的是，成功解偶联抗病毒沉默的触发物和靶标将允许探索动物王国中由viRNA介导的病毒-宿主相互作用的新特征。
Small interfering RNAs (siRNAs) processed from viral replication intermediates by RNase III-like enzyme Dicer guide sequence-specific antiviral silencing in fungi, plants, and invertebrates. In plants, virus-derived siRNAs (viRNAs) can target and silence cellular transcripts and, in some cases, are responsible for the induction of plant diseases. Currently it remains unclear whether viRNAs are also capable of modulating the expression of cellular genes in the animal kingdom, although animal virus-encoded microRNAs (miRNAs) are known to guide efficient silencing of host genes, thereby facilitating virus replication. In this report, we showed that viRNAs derived from a modified nodavirus triggered potent silencing of homologous cellular transcripts produced by the endogenous gene or transgene in the nematode worm Caenorhabditis elegans. Like that found in plants, virus-induced gene silencing (VIGS) in C. elegans also involves RRF-1, a worm RNA-dependent RNA polymerase (RdRP) that is known to produce single-stranded secondary siRNAs in a Dicer-independent manner. We further demonstrated that VIGS in C. elegans is inheritable, suggesting that VIGS has the potential to generate profound epigenetic consequences in future generations. Altogether, these findings, for the first time, confirmed that viRNAs have the potential to modulate host gene expression in the animal kingdom. Most importantly, the success in uncoupling the trigger and the target of the antiviral silencing would allow for the exploration of novel features of virus-host interactions mediated by viRNAs in the animal kingdom.