PDF(Pubmed)
Abstract：
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact worldwide. Mapping virus-host interactions is critical to understand disease progression. MicroRNAs (miRNAs) are important RNA regulators, but their interaction with SARS-CoV-2 RNA was not experimentally investigated. Here, using Argonaute (AGO) cross-linking immunoprecipitation combined with RNA proximity ligation (CLEAR-CLIP), we provide unbiased mapping of SARS-CoV-2/miRNA interactions. We identified six main regions on the viral RNA bound primarily by one specific miRNA. Targeted mutagenesis and AGO1-3 knockdown demonstrated that these interactions are not critical for virus production. Moreover, we identified perturbed regulation of cellular miRNA interactions during infection, including non-compensated viral sequestration of the miR-15 family. Transcriptome analysis further showed that mRNAs targeted by this miRNA family are derepressed. This work delineates the interphase between miRNA regulation and SARS-CoV-2 infection and further contributes to deciphering the full molecular interactome of this virus.
摘要：
严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）大流行在全球范围内产生了巨大影响。绘制病毒-宿主相互作用图对于了解疾病进展至关重要。microRNAs(miRNAs)是重要的RNA调节因子,但是它们与SARS-CoV-2RNA的相互作用没有实验研究。这里,使用Argonaute（AGO）交联免疫沉淀结合RNA邻近连接（CLEAR-CLIP），我们提供了SARS-CoV-2/miRNA相互作用的无偏图谱。我们确定了病毒RNA上的六个主要区域，主要由一个特定的miRNA结合。靶向诱变和AGO1-3敲低表明这些相互作用对于病毒生产不是关键的。此外，我们确定了感染过程中细胞miRNA相互作用的扰动调节，包括miR-15家族的非代偿性病毒隔离。转录组分析进一步显示该miRNA家族靶向的mRNA被去抑制。这项工作描述了miRNA调控与SARS-CoV-2感染之间的间期，并进一步有助于破译该病毒的完整分子相互作用组。
