Genome-Wide Identification of Circular RNAs Revealed the Dominant Intergenic Region Circularization Model in Apostichopus japonicus
Genome-Wide Identification of Circular RNAs Revealed the Dominant Intergenic Region Circularization Model in Apostichopus japonicus
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DOI：
10.3389/fgene.2019.00603
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发表时间：
2019-07
影响因子：
3.7
通讯作者：
Xuelin Zhao;Xuemei Duan;Jianping Fu;Y. Shao;Weiwei Zhang;M. Guo;Chenghua Li
中科院分区：
文献类型：
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作者：
Xuelin Zhao;Xuemei Duan;Jianping Fu;Y. Shao;Weiwei Zhang;M. Guo;Chenghua Li
环状RNA（circular RNA，circRNA）作为竞争性内源RNA参与基因表达调控。先前对人类和蚕的研究表明，circRNA参与免疫调节。在这里，我们进行了体腔细胞circRNA测序，以探讨其在健康和皮肤溃疡综合征（SUS）患病海参的免疫功能。与动物模型相比，在具有多样化环化模式的文库中总共鉴定了3，592个circRNA。常见的内含子配对驱动的环化模型在海参基因组中已不再流行，取而代之的是基因间区域环化。通过桑格测序和RNA酶R处理的测定进一步验证这些鉴定的circRNA的准确性。表达谱分析显示，在SUS病组中，有117个circRNA表达上调，144个circRNA表达下调，其中71.6%为基因间型circRNA。构建了差异表达的circRNA和microRNA（miRNAs）的相互作用网络，结果显示，在先前研究中检测到的SUS患者中存在显著差异表达的miR-2008和miR-31分别受到10个和11个具有10个以上结合位点的差异表达circRNA的调控。此外，还对7种circRNA进行了实时定量PCR验证，其变异趋势与circRNA测序结果一致。这些结果支持基因间型circRNA可能通过作为miRNA调控因子在刺参免疫应答中发挥主导作用。
Circular RNAs (circRNAs) were recently recognized to act as competing endogenous RNAs and play roles in gene expression regulation. Previous studies in humans and silkworms have shown that circRNAs take part in immune regulation. Here, we conducted coelomocyte circRNA sequencing to explore its immune functions in healthy and skin ulceration syndrome (SUS)-diseased sea cucumbers. A total of 3,592 circRNAs were identified in libraries with diversified circularization patterns compared with animal models. The common intron-pairing-driven circularization models are not popular in sea cucumber genome, which was replaced with intergenic region circularization. The accuracy of these identified circRNAs was further validated by Sanger sequencing and RNase R-treated assays. Expression profile analysis indicated that 117 circRNAs were upregulated and 144 circRNAs were downregulated in SUS-diseased condition, of which 71.6% were intergenic-type circRNAs. The interaction network of differentially expressed circRNAs and microRNAs (miRNAs) was constructed and showed that miR-2008 and miR-31, detected with significantly differential expression in SUS-affected samples in a previous study, were predicted to be regulated by 10 and 11 differentially expressed circRNAs with more than 10 binding sites, respectively. Moreover, seven circRNAs were further validated by quantitative real-time PCR, whose variation trends were consistent with circRNA sequencing. All our results supported that intergenic-type circRNAs might have a dominant function in Apostichopus japonicas immune response by acting as miRNA regulators.