Department of Virology, Medical University of Vienna, Vienna, Austria.
Nucleic Acids Res. 2010 Dec;38(22):8328-37. doi: 10.1093/nar/gkq681. Epub 2010 Aug 12.
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a pivotal role in the regulation of posttranscriptional gene expression in a wide range of eukaryotic organisms. Although DNA viruses have been shown to encode miRNAs and exploit the cellular RNA silencing machinery as a convenient way to regulate viral and host gene expression, it is generally believed that this pathway is not available to RNA viruses that replicate in the cytoplasm of the cell because miRNA biogenesis is initiated in the nucleus. In fact, among the >200 viral miRNAs that have been experimentally verified so far, none is derived from an RNA virus. Here, we show that a cytoplasmic RNA virus can indeed encode and produce a functional miRNA. We introduced a heterologous miRNA-precursor stem-loop sequence element into the RNA genome of the flavivirus tick-borne encephalitis virus, and this led to the production of a functional miRNA during viral infection without impairing viral RNA replication. These findings demonstrate that miRNA biogenesis can be used by cytoplasmic RNA viruses to produce regulatory molecules for the modulation of the transcriptome.
微小 RNA（miRNA）是一类小型非编码 RNA，在真核生物中转录后基因表达的调控中起着关键作用。尽管已经表明 DNA 病毒可以编码 miRNA，并利用细胞 RNA 沉默机制作为一种方便的方式来调节病毒和宿主基因表达，但人们普遍认为，这种途径不适用于在细胞质中复制的 RNA 病毒，因为 miRNA 的生物发生是在细胞核中开始的。事实上，在迄今为止已被实验验证的超过 200 种病毒 miRNA 中，没有一种是源自 RNA 病毒。在这里，我们表明一种细胞质 RNA 病毒确实可以编码并产生功能性 miRNA。我们将异源 miRNA 前体茎环序列元件引入黄病毒蜱传脑炎病毒的 RNA 基因组中，这导致在病毒感染期间产生了功能性 miRNA，而不会损害病毒 RNA 复制。这些发现表明，细胞质 RNA 病毒可以利用 miRNA 的生物发生来产生调节分子，以调节转录组。
