Virus-derived circular RNAs populate hepatitis C virus-infected cells.
Virus-derived circular RNAs populate hepatitis C virus-infected cells.
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DOI：
10.1073/pnas.2313002121
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发表时间：
2024-02
影响因子：
11.1
通讯作者：
Qian M Cao;Pakpoom Boonchuen;Tzu-Chun Chen;Shaohua Lei;Kunlaya Somboonwiwat;P. Sarnow
中科院分区：
文献类型：
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作者：
Qian M Cao;Pakpoom Boonchuen;Tzu-Chun Chen;Shaohua Lei;Kunlaya Somboonwiwat;P. Sarnow
已知真核细胞中的前mRNA可以通过反向剪接机制加工成环状RNA。环状RNA具有很大的稳定性，可以螯合蛋白质或小RNA，从而在细胞通路上发挥功能。由于病毒经常利用宿主途径，我们探索了胞质丙型肝炎病毒的RNA基因组是否被加工以产生病毒衍生的circRNA（vcircRNA）。RNA-seq实验的计算分析预测，病毒RNA基因组被片段化以产生数百个vcircRNA。其中有十几个是通过滚环放大实验验证的。发现含有病毒内部核糖体进入位点的VcircRNA被翻译成显示前病毒功能的蛋白质。此外，两种高度丰富的非翻译vcircRNA显示出增强病毒RNA丰度。这些发现表明，新的vcircRNA分子调节细胞质RNA病毒感染的细胞中的病毒扩增。
It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.