title: Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis.
abstract: 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.
authors: Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors: Jing
authors: J
authors: Gong
authors: Yin
authors: Y
authors: Tong
authors: Hong-Mei
authors: HM
authors: Zhang
authors: Kai
authors: K
authors: Wang
authors: Tao
authors: T
authors: Hu
authors: Ge
authors: G
authors: Shan
authors: Jun
authors: J
authors: Sun
authors: An-Yuan
authors: AY
authors: Guo
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D008156:Luciferases