Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts.
Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts.
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DOI：
10.1128/spectrum.01106-22
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发表时间：
2022-06-29
影响因子：
3.7
通讯作者：
Zhu, Hua
中科院分区：
文献类型：
--
作者：
Yang, Shaomin;Liu, Xiaolian;Wang, Mei;Cao, Di;Jaijyan, Dabbu Kumar;Enescu, Nicole;Liu, Jian;Wu, Songbin;Wang, Sashuang;Sun, Wuping;Xiao, Lizu;Gu, Alison;Li, Yaolan;Zhou, Hong;Tyagi, Sanjay;Wu, Jianguo;Tang, Qiyi;Zhu, Hua
人巨细胞病毒（HCMV）感染全球大部分人群。一些HCMV衍生的非编码RNA参与病毒基因表达和病毒生命周期的调节。在这里，我们报道了circRNA是一类新的HCMV转录本。我们生物信息学预测704个候选circRNA编码的TB 40/E菌株和230编码的HAN菌株。我们还系统地比较了宿主基因组编码的circRNA和病毒circRNA之间的circRNA特征，包括断点序列的一致性、链偏好性、长度分布和外显子数目，并表明病毒circRNA的独特特征与其基因组类型相关。此外，我们实验证实了324个反向剪接连接（BSJs）从三个HCMV株，Towne，TB 40/E，托莱多，并确定了4个代表性的HCMV circRNA的RNase R处理。有趣的是，我们还发现HCMV含有选择性反向剪接的circRNA。我们开发了一种新的扩增FISH方法，使我们能够可视化circRNA并量化感染细胞中circRNA分子的数量。竞争性内源RNA网络分析表明，HCMV circRNA通过circRNA-miRNA-mRNA网络在病毒DNA合成中发挥重要作用。我们的研究结果强调，circRNA是HCMV转录组的重要组成部分，可能有助于病毒复制和发病机制。重要性HCMV感染全球40%至100%的人群，并且可能是免疫功能低下个体的危及生命的病原体。CircRNA是一个独特的RNA家族，是最新发现的，在许多方面仍然未知。我们目前的研究通过计算鉴定了HCMV编码的circRNA，并证实了HCMV circRNA在感染细胞中的存在。我们系统地比较了宿主与不同病毒circRNA之间的特征，发现circRNA的独特特征与其基因组类型相关。我们还首次报道了HCMV含有选择性反向剪接的circRNA。更重要的是，我们开发了一种新的扩增FISH方法，这不仅使我们首次能够可视化circRNA，而且还可以量化感染细胞中circRNA分子的数量。这项工作描述了HCMV转录组的一个新的组成部分，带来了对HCMV生物学和疾病的新认识。
Human cytomegalovirus (HCMV) infects a large portion of the human population globally. Several HCMV-derived noncoding RNAs are involved in the regulation of viral gene expression and the virus life cycle. Here, we reported that circRNAs are a new class of HCMV transcripts. We bioinformatically predict 704 candidate circRNAs encoded by the TB40/E strain and 230 encoded by the HAN strain. We also systematically compare circRNA features, including the breakpoint sequence consensus, strand preference, length distribution, and exon numbers between host genome-encoded circRNAs and viral circRNAs, and showed that the unique characteristics of viral circRNAs are correlated with their genome types. Furthermore, we experimentally confirmed 324 back-splice junctions (BSJs) from three HCMV strains, Towne, TB40/E, and Toledo, and identified 4 representative HCMV circRNAs by RNase R treatment. Interestingly, we also showed that HCMV contains alternative back-splicing circRNAs. We developed a new amplified FISH method that allowed us to visualize circRNAs and quantify the number of circRNA molecules in the infected cells. The competitive endogenous RNA network analysis suggests that HCMV circRNAs play important roles in viral DNA synthesis via circRNA-miRNA-mRNA networks. Our findings highlight that circRNAs are an important component of the HCMV transcriptome that may contribute to viral replication and pathogenesis. IMPORTANCE HCMV infects 40% to 100% of the human population globally and may be a life-threatening pathogen in immunocompromised individuals. CircRNA is a family of unique RNA that is the most newly found and remains unknown in many aspects. Our current studies computationally identified HCMV-encoded circRNAs and confirmed the existence of the HCMV circRNAs in the infected cells. We systematically compared the features between host and different viral circRNAs and found that the unique characteristics of circRNAs were correlated with their genome types. We also first reported that HCMV contained alternative back-splicing circRNAs. More importantly, we developed a new amplified FISH method which allowed us for the first time not only to visualize circRNAs but also to quantify the number of circRNA molecules in the infected cells. This work describes a novel component of HCMV transcriptome bringing a new understanding of HCMV biology and disease.
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通讯作者：
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