Genome-Wide Identification of SNPs in MicroRNA Genes and the SNP Effects on MicroRNA Target Binding and Biogenesis
Genome-Wide Identification of SNPs in MicroRNA Genes and the SNP Effects on MicroRNA Target Binding and Biogenesis
复制标题
microRNA 基因中 SNP 的全基因组鉴定以及 SNP 对 microRNA 靶标结合和生物发生的影响
DOI：
10.1002/humu.21641
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发表时间：
2012-01-01
期刊：
影响因子：
3.9
通讯作者：
Guo, An-Yuan
中科院分区：
文献类型：
--
作者：
Gong, Jing;Tong, Yin;Guo, An-Yuan
microRNAs（miRNAs）是参与不同疾病的基因表达的关键调控因子。miRNA基因或靶位点的多个单核苷酸多态性（single nucleotide polymorphism，SNPs）（miRNA-related SNPs）已被证实通过影响miRNA介导的调控功能与人类疾病相关。为了系统地分析miRNA相关的SNPs及其作用，我们对人类pre-miRNA、miRNA侧翼区、靶位点的SNPs进行了全基因组扫描，并设计了一个预测它们对miRNA-靶相互作用的影响的管道。结果，我们在人类miRNA种子区鉴定了48个SNP，在3'非翻译区鉴定了数千个SNP，这些SNP可能干扰或产生miRNA-靶标相互作用。此外，我们通过荧光素酶试验证实了7个功能丧失的SNP和1个功能获得的SNP。这是实验验证miRNA中的SNP产生新的miRNA靶结合的第一例。所有有用的数据都被编入miRNASNP，这是一个用户友好的免费在线数据库（http：//www.miRNASNP/）。这些数据将为研究miRNA的功能，识别疾病相关的miRNA以及进一步的个性化医疗提供有用的资源。Mutat 33：254-263，2012. (C)2011 Wiley Periodicals，Inc.
MicroRNAs (miRNAs) are studied as key regulators of gene expression involved in different diseases. Several single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA-mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites, and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3' untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed seven loss-of-function SNPs and one gain-of-function SNP by luciferase assay. This is the first case of experimental validation of an SNP in an miRNA creating a novel miRNA target binding. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine. Hum Mutat 33: 254-263, 2012. (C) 2011 Wiley Periodicals, Inc.