Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection
Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection
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DOI：
10.7717/peerj.9369
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发表时间：
2020-06-05
期刊：
影响因子：
2.7
通讯作者：
Adan, Aysun
中科院分区：
文献类型：
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作者：
Demirci, Muserref Duygu Sacar;Adan, Aysun
MicroRNAs(MiRNAs)是基因表达的转录后调节因子，存在于200多种不同的生物体中。虽然目前还不完全确定RNA病毒是否能产生miRNAs，但已经有来自RNA病毒的具有调节功能的miRNA样序列的例子。在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中，有几种机制可以使miRNAs影响病毒，如干扰病毒的复制、翻译，甚至调节宿主的表达。在这项研究中，我们对SARS-CoV-2基因组进行了基于机器学习的miRNA预测分析，以识别类似miRNA的发夹，并寻找病毒miRNAs与人类基因以及人miRNAs与病毒基因之间潜在的基于miRNA的相互作用。总共从病毒基因组中提取了950个发夹结构的序列，根据预测结果，其中29个可能是前体miRNAs。靶向分析表明，30个病毒成熟的miRNA样序列可以靶向1367个不同的人类基因。Panther基因功能分析结果表明，病毒来源的miRNA候选基因可以靶向参与关键细胞过程的各种基因，包括转录、代谢、防御系统和几个信号通路，如Wnt和EGFR信号。基于蛋白质类的目标人类基因分组表明，宿主转录可能是病毒的主要靶标之一，因为参与转录过程的96个基因是预测的病毒miRNAs的潜在靶标。例如，包括人类介体复合体(MED_1、MED_9、MED_(12)L、MED_(19))几个组分的基础转录机制元件、基础转录因子(如TAF4、TAF5、TAF7L)和位点特异性转录因子(如STATI)被发现是靶标。此外，许多已知的人类miRNAs似乎能够靶向参与病毒生命周期的病毒基因，如S、M、N、E蛋白和ORFLab、ORF3a、ORF8、ORF7a和ORF10。鉴于基于miRNA的治疗已经受到重视，根据本研究的结果，了解miRNA的作用模式及其在SARS-CoV-2感染中可能发挥的作用，可以为新的治疗方法的开发和改进创造新的机遇。
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs, there are examples of miRNA like sequences from RNA viruses with regulatory functions. In the case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with viral replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA-based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Overall, 950 hairpin structured sequences were extracted from the virus genome and based on the prediction results, 29 of them could be precursor miRNAs. Targeting analysis showed that 30 viral mature miRNA-like sequences could target 1,367 different human genes. PANTHER gene function analysis results indicated that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription, metabolism, defense system and several signaling pathways such as Wnt and EGFR signalings. Protein class-based grouping of targeted human genes showed that host transcription might be one of the main targets of the virus since 96 genes involved in transcriptional processes were potential targets of predicted viral miRNAs. For instance, basal transcription machinery elements including several components of human mediator complex (MED1, MED9, MED 12L, MED 19), basal transcription factors such as TAF4, TAF5, TAF7L and site-specific transcription factors such as STATI were found to be targeted. In addition, many known human miRNAs appeared to be able to target viral genes involved in viral life cycle such as S, M, N, E proteins and ORF lab, ORF3a, ORF8, ORF7a and ORF10. Considering the fact that miRNA-based therapies have been paid attention, based on the findings of this study, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics.