Brief Bioinform. 2021 Mar 22;22(2):2182-2190. doi: 10.1093/bib/bbaa052.
Circular RNAs (circRNAs) are covalently closed long noncoding RNAs critical in diverse cellular activities and multiple human diseases. Several cancer-related viral circRNAs have been identified in double-stranded DNA viruses (dsDNA), yet no systematic study about the viral circRNAs has been reported. Herein, we have performed a systematic survey of 11 924 circRNAs from 23 viral species by computational prediction of viral circRNAs from viral-infection-related RNA sequencing data. Besides the dsDNA viruses, our study has also revealed lots of circRNAs in single-stranded RNA viruses and retro-transcribing viruses, such as the Zika virus, the Influenza A virus, the Zaire ebolavirus, and the Human immunodeficiency virus 1. Most viral circRNAs had reverse complementary sequences or repeated sequences at the flanking sequences of the back-splice sites. Most viral circRNAs only expressed in a specific cell line or tissue in a specific species. Functional enrichment analysis indicated that the viral circRNAs from dsDNA viruses were involved in KEGG pathways associated with cancer. All viral circRNAs presented in the current study were stored and organized in VirusCircBase, which is freely available at http://www.computationalbiology.cn/ViruscircBase/home.html and is the first virus circRNA database. VirusCircBase forms the fundamental atlas for the further exploration and investigation of viral circRNAs in the context of public health.
环状 RNA（circRNAs）是共价闭合的长非编码 RNA，在多种细胞活动和多种人类疾病中起关键作用。已经在双链 DNA 病毒（dsDNA）中鉴定出几种与癌症相关的病毒 circRNAs，但尚未有关于病毒 circRNAs 的系统研究报道。在此，我们通过计算预测病毒感染相关 RNA 测序数据中的病毒 circRNAs，对来自 23 种病毒的 11924 个 circRNAs 进行了系统调查。除了 dsDNA 病毒外，我们的研究还揭示了许多单链 RNA 病毒和逆转录病毒中的 circRNAs，如寨卡病毒、甲型流感病毒、扎伊尔埃博拉病毒和人类免疫缺陷病毒 1。大多数病毒 circRNAs 在侧翼拼接位点的反向互补序列或重复序列。大多数病毒 circRNAs 仅在特定物种的特定细胞系或组织中表达。功能富集分析表明，dsDNA 病毒的 circRNAs 参与了与癌症相关的 KEGG 途径。本研究中呈现的所有病毒 circRNAs 都存储在 VirusCircBase 中，并组织在 VirusCircBase 中，网址为：http://www.computationalbiology.cn/ViruscircBase/home.html，这是第一个病毒 circRNA 数据库。VirusCircBase 为进一步探索和研究公共卫生背景下的病毒 circRNAs 提供了基础图谱。
