Dehghanzad Reyhaneh, Panahi Moghadam Somayeh, Shirvani Farsani Zeinab
Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Cellular and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Adv Biomed Res. 2021 Feb 26;10:8. doi: 10.4103/abr.abr_143_20. eCollection 2021.
Different genetic variants, including the single-nucleotide polymorphisms (SNPs) present in microRNA recognition elements (MREs) within 3'UTR of genes, can affect miRNA-mediated gene regulation and susceptibility to a variety of human diseases such as multiple sclerosis (MS), a disease of the central nervous system. Since the expression of many genes associated with MS is controlled by microRNAs (miRNAs), the aim of this study was to analyze SNPs within miRNA binding sites of some neuronal genes associated with MS.
Fifty-seven neuronal genes related to MS were achieved using dbGaP, DAVID, DisGeNET, and Oviddatabases. 3'UTR of candidate genes were assessed for SNPs, and miRNAs' target prediction databases were used for predicting miRNA binding sites.
Three hundred and eight SNPs (minor allele frequency >0.05) were identified in miRNA binding sites of 3'UTR of 44 genes. Among them, 42 SNPs in 22 genes had miRNA binding sites and miRNA prediction tools suggested 71 putative miRNAs binding sites on these genes. Moreover, analysis predicted 22 MRE-modulating SNPs and 22 MRE-creating SNPs in the 3'UTR of these candidate genes.
These candidate MRE-SNPs can alter miRNAs binding sites and mRNA gene regulation. Therefore, these genetic variants and miRNAs might be involved in MS susceptibility and pathogenesis and hence would be valuable for further functional verification investigation.
不同的基因变异，包括基因3'非翻译区（3'UTR）内微小RNA识别元件（MRE）中的单核苷酸多态性（SNP），可影响微小RNA介导的基因调控以及对多种人类疾病的易感性，如中枢神经系统疾病多发性硬化症（MS）。由于许多与MS相关的基因表达受微小RNA（miRNA）控制，本研究旨在分析一些与MS相关的神经元基因的miRNA结合位点内的SNP。
使用dbGaP、DAVID、DisGeNET和Ovid数据库获取57个与MS相关的神经元基因。评估候选基因的3'UTR中的SNP，并使用miRNA靶标预测数据库预测miRNA结合位点。
在44个基因的3'UTR的miRNA结合位点中鉴定出308个SNP（次要等位基因频率>0.05）。其中，22个基因中的42个SNP具有miRNA结合位点，miRNA预测工具表明这些基因上有71个推定的miRNA结合位点。此外，分析预测这些候选基因的3'UTR中有22个MRE调节SNP和22个MRE产生SNP。
这些候选MRE-SNP可改变miRNA结合位点和mRNA基因调控。因此，这些基因变异和miRNA可能参与MS的易感性和发病机制，因此对进一步的功能验证研究具有重要价值。
