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通过计算方法预测位点定向微小RNA作为转录调节因子对抗丙型流感病毒感染的关键参与者。

Prediction of Site Directed miRNAs as Key Players of Transcriptional Regulators Against Influenza C Virus Infection Through Computational Approaches.

作者信息

Hassan Mubashir, Iqbal Muhammad Shahzad, Naqvi Sawaira, Alashwal Hany, Moustafa Ahmed A, Kloczkowski Andrzej

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children Hospital, Columbus, OH, United States.

出版信息

Front Mol Biosci. 2022 Apr 8;9:866072. doi: 10.3389/fmolb.2022.866072. eCollection 2022.

DOI:10.3389/fmolb.2022.866072
PMID:35463952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9023806/
Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene expression, cell differentiation, and immunity against viral infections. In this study, we have used the computational tools, RNA22, RNAhybrid, and miRanda, to predict the microRNA-mRNA binding sites to find the putative microRNAs playing role in the host response to influenza C virus infection. This computational research screened the following four miRNAs: hsa-mir-3155a, hsa-mir-6796-5p, hsa-mir-3194-3p and hsa-mir-4673, which were further investigated for binding site prediction to the influenza C genome. Moreover, multiple sites in protein-coding region (HEF, CM2, M1-M2, NP, NS1- NS2, NSF, P3, PB1 and PB2) were predicted by RNA22, RNAhybrid and miRanda. Furthermore, 3D structures of all miRNAs and HEF were predicted and checked for their binding potential through molecular docking analysis. The comparative results showed that among all proteins, HEF is higher in prevalence throughout the analysis as a potential (human-derived) microRNAs target. The target-site conservation results showed that core nucleotide sequence in three different strains is responsible for potential miRNA binding to different viral strains. Further steps to use these microRNAs may lead to new therapeutic insights on fighting influenza virus infection.

摘要

微小RNA（miRNA）是一类小的非编码RNA，在基因表达、细胞分化以及抗病毒感染免疫中发挥关键作用。在本研究中，我们使用了RNA22、RNAhybrid和miRanda等计算工具来预测微小RNA与信使RNA的结合位点，以寻找在宿主对丙型流感病毒感染的反应中发挥作用的假定微小RNA。这项计算研究筛选出了以下四种微小RNA：hsa - mir - 3155a、hsa - mir - 6796 - 5p、hsa - mir - 3194 - 3p和hsa - mir - 4673，并对它们与丙型流感病毒基因组的结合位点预测进行了进一步研究。此外，RNA22、RNAhybrid和miRanda还预测了蛋白质编码区（血凝素 - 酯酶融合蛋白、CM2、基质蛋白1 - 基质蛋白2、核蛋白、非结构蛋白1 - 非结构蛋白2、核纤层蛋白、P3、PB1和PB2）中的多个位点。此外，还预测了所有微小RNA和血凝素 - 酯酶融合蛋白的三维结构，并通过分子对接分析检查了它们的结合潜力。比较结果表明，在所有蛋白质中，血凝素 - 酯酶融合蛋白在整个分析过程中作为潜在的（人源）微小RNA靶点的出现频率更高。靶点位点保守性结果表明，三种不同毒株中的核心核苷酸序列负责潜在微小RNA与不同病毒毒株的结合。使用这些微小RNA的进一步步骤可能会为对抗流感病毒感染带来新的治疗思路。

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