College of Chemistry, Chemical Engineering, and Biotechnology, Donghua University, Shanghai, 201620, China.
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, United States.
Sci Rep. 2020 Apr 1;10(1):5789. doi: 10.1038/s41598-020-62588-6.
MicroRNAs are widely referred to as gene expression regulators for different diseases. The integration between single nucleotide polymorphisms (SNPs) and miRNAs has been associated with both human and animal diseases. In order to gain new insights on the effects of SNPs on miRNA and their related sequences, we steadily characterized a whole mouse genome miRNA related SNPs, analyzed their effects on the miRNA structural stability and target alteration. In this study, we collected 73643859 SNPs across the mouse genome, analyzed 1187 pre-miRNAs and 2027 mature miRNAs. Upon mapping the SNPs, 1700 of them were identified in 702 pre-miRNAs and 609 SNPs in mature miRNAs. We also discovered that SNP densities of the pre-miRNA and mature miRNAs are lower than the adjacent flanking regions. Also the flanking regions far away from miRNAs appeared to have higher SNP density. In addition, we also found that transitions were more frequent than transversions in miRNAs. Notably, 841 SNPs could change their corresponding miRNA's secondary structure from stable to unstable. We also performed target gain and loss analysis of 163 miRNAs and our results showed that few miRNAs remained unchanged and many miRNAs from wild mice gained target site. These results outline the first case of SNP variations in the mouse whole genome scale. Those miRNAs with changes in structure or target could be of interest for further studies.
微小 RNA 通常被称为不同疾病的基因表达调控因子。单核苷酸多态性 (SNP) 与 miRNA 的整合与人类和动物疾病都有关。为了深入了解 SNP 对 miRNA 及其相关序列的影响,我们对整个小鼠基因组 miRNA 相关 SNP 进行了系统表征,分析了它们对 miRNA 结构稳定性和靶标改变的影响。在这项研究中,我们收集了整个小鼠基因组中的 73643859 个 SNP,分析了 1187 个前体 miRNA 和 2027 个成熟 miRNA。在对 SNP 进行映射后,在 702 个前体 miRNA 中发现了 1700 个 SNP,在 609 个成熟 miRNA 中发现了 609 个 SNP。我们还发现,前体 miRNA 和成熟 miRNA 的 SNP 密度低于相邻侧翼区域。此外,远离 miRNA 的侧翼区域似乎具有更高的 SNP 密度。另外,我们还发现 miRNA 中转换的频率高于颠换。值得注意的是,841 个 SNP 可以使它们对应的 miRNA 的二级结构从稳定变为不稳定。我们还对 163 个 miRNA 进行了靶标增益和损失分析,结果表明,很少有 miRNA 保持不变,许多野生型小鼠的 miRNA 获得了靶标位点。这些结果概述了 SNP 变异在小鼠全基因组范围内的首例情况。那些结构或靶标发生变化的 miRNA 可能是进一步研究的对象。