He Sha, Ou Haiyan, Zhao Cunyou, Zhang Jian
Bioinformatics Section, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Int J Genomics. 2018 Mar 6;2018:2456076. doi: 10.1155/2018/2456076. eCollection 2018.
miRNAs are a class of noncoding RNAs important in posttranscriptional repressors and involved in the regulation of almost every biological process by base paring with target genes through sequence in their seed regions. Genetic variations in the seed regions have vital effects on gene expression, phenotypic variation, and disease susceptibility in humans. The distribution pattern of genetic variation in miRNA seed regions might be related to miRNA function and is worth paying more attention to. We here employed computational analyses to explore the clustering pattern and functional effect of SNPs in human miRNA seed regions. A total of 1879 SNPs were mapped to 1226 human miRNA seed regions. We found that miRNAs with SNPs in their seed region are significantly enriched in miRNA clusters. We also found that SNPs in clustered miRNA seed regions have a lower functional effect than have SNPs in nonclustered miRNA seed regions. Additionally, we found that clustered miRNAs with SNPs in seed regions are involved in more pathways. Overall, our results demonstrate that SNPs in clustered miRNA seed regions can take part in more intricate and complex gene-regulating networks with lower functional cost by functional complementarity. Moreover, our results also broaden current knowledge on the genetic variation in human miRNA seed regions.
微小RNA（miRNA）是一类在转录后发挥重要作用的非编码RNA，通过其种子区域的序列与靶基因进行碱基配对，参与几乎所有生物过程的调控。种子区域的基因变异对人类基因表达、表型变异和疾病易感性具有至关重要的影响。miRNA种子区域基因变异的分布模式可能与miRNA功能相关，值得更多关注。我们在此采用计算分析方法来探究人类miRNA种子区域单核苷酸多态性（SNP）的聚类模式和功能效应。总共1879个SNP被定位到1226个人类miRNA种子区域。我们发现，种子区域存在SNP的miRNA在miRNA簇中显著富集。我们还发现，成簇miRNA种子区域中的SNP比非成簇miRNA种子区域中的SNP具有更低的功能效应。此外，我们发现种子区域存在SNP的成簇miRNA参与更多的信号通路。总体而言，我们的结果表明，成簇miRNA种子区域中的SNP可通过功能互补参与更复杂的基因调控网络，且功能成本更低。此外，我们的结果还拓宽了目前关于人类miRNA种子区域基因变异的认识。
