Identification and characterization of circular RNAs in the silkworm midgut following Bombyx mori cytoplasmic polyhedrosis virus infection
Identification and characterization of circular RNAs in the silkworm midgut following Bombyx mori cytoplasmic polyhedrosis virus infection
复制标题
家蚕细胞质多角体病毒感染后家蚕中肠中环状 RNA 的鉴定和表征。
DOI：
10.1080/15476286.2017.1411461
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Gong, Chengliang
中科院分区：
文献类型：
--
作者：
Hu, Xiaolong;Zhu, Min;Gong, Chengliang
家蚕胞质多角体病毒（BmCPV）感染的发病机制尚不清楚，尽管越来越多的证据表明，环状rna （circRNAs）作为竞争性内源性rna或正调节因子，在真核生物中调节基因表达发挥重要作用，因此可能在BmCPV感染中发挥作用。为了探索BmCPV感染后家蚕中肠中circRNA的表达和生物学功能，我们采用高通量测序技术测定了正常家蚕中肠组织（对照）和感染BmCPV的家蚕中肠组织（试验）的circRNA表达谱。从对照和测试样本中分别检测到9753和7475个circrna。这两个样本共有6085个circrna，而在对照和测试样本中分别有646个和737个circrna特异性表达。共发现3638个circrna存在差异表达，其中400个circrna存在显著差异表达，差异表达倍数为2.0 (p< 0.05，假发现率< 0.05)，其中感染后上调294个，下调106个。通过基因本体和京都基因与基因组百科全书途径富集分析，确定了差异调控基因的主要功能。基于差异表达的circrna与其microRNA （miRNA）结合位点的性质之间的相关性分析，构建了circRNA-miRNA相互作用网络。该网络推断，在300种最丰富的关系中，有13种mirna与193种circrna相互作用。bmo-miR-3389-5p、bmo-miR-745-3p和bmo-miR-3262分别与30,34和34个circrna相关。circRNA_8115、circRNA_9444、circRNA_4553、circRNA_0827和circRNA_6649分别含有6个、5个、4个、4个和4个miRNA结合位点。我们进一步发现，circrna的选择性环状化是家蚕的一个共同特征，许多家蚕circrna的连接位点两侧都有典型的GT/AG剪接信号。我们的研究首次展示了circRNA对病毒感染的反应。从而为研究BmCPV发病过程中circRNA-miRNA相互作用提供了新的视角，为进一步研究circrna在BmCPV发病过程中的潜在作用奠定了基础。
The pathogenesis of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection is unclear, although accumulating evidence indicates that circular RNAs (circRNAs), which act as competing endogenous RNAs or positive regulators, play important roles in regulating gene expression in eukaryotes and, thus, may play a role in BmCPV infections. To explore the expression and biological functions of circRNAs in the silkworm midgut following BmCPV infection, silkworm circRNA expression profiles of normal midgut tissue (control) and BmCPV-infected midgut tissue (test) were determined using high-through sequencing. A total of 9,753 and 7,475circRNAs were detected from the control and test samples, respectively. The two samples shared 6,085 circRNAs, while 646 and 737 circRNAs were expressed specifically in the control and test samples, respectively. A total of 3,638 circRNAs were shown to be differentially expressed, and 400 circRNAs were substantially differentially expressed with a fold-change 2.0 (p< 0.05 and a false discover rate < 0.05), of which 294 were up-regulated and 106 were down-regulated following infection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to determine the principal functions of the substantially differentially regulated genes. circRNA-miRNA interaction networks were constructed based on a correlation analysis between the differentially expressed circRNAs and the nature of their microRNA (miRNA) binding sites. The network inferred that 13 miRNAs interacting with 193 circRNAs were among the 300 most abundant relationships. bmo-miR-3389-5p, bmo-miR-745-3p, and bmo-miR-3262 were related to 30, 34, and 34 circRNAs, respectively. circRNA_8115, circRNA_9444, circRNA_4553, circRNA_0827, and circRNA_6649 contained six, five, four, four, and four miRNA binding sites, respectively. We further found that alternative circularization of circRNAs is a common feature in silkworms and that the junction sites of many silkworm circRNAs are flanked by canonical GT/AG splicing signals. Our study is the first to show the circRNA response to virus infection. Thus, it provides a novel perspective on circRNA-miRNA interactions during BmCPV pathogenesis, and it lays the foundation for future research of the potential roles of circRNAs in BmCPV pathogenesis.