MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs

Abstract

BackgroundNumerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers.DescriptionWe developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research.ConclusionMirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…The organisation of the genes encoding miRNAs allows for the activity of polymerases II and III which are both involved in transcribing genes encoding small RNAs [38,39]. However, regions encoding pre-miRNA sequences have been shown to contain approximately 2000 single nucleotide polymorphisms (SNPs) which may affect miRNA-mRNA interactions [40]. Genetic alterations in miRNA sequences are likely to affect their regulatory activity and, consequently, a number of cellular processes including carcinogenesis [41].…”

Inferring Single Nucleotide Polymorphisms in MicroRNA Binding Sites of Lung Cancer-related Inflammatory Genes

“…The commonly rule in the method is that nucleotides 6-8 in the 5' end of the miRNA (called as 'seed' sequences) provide the maximal binding free energy of the miRNA-target duplex and the G:T pairing is admitted in the miRNA-target (John et al, 2004;Tomari et al, 2005). The most studies predict SNPs within miRNA binding sites and assess the potential functions of SNPs in 3'UTR via well-developed algorithms, based on the differences in the alignment scores and variations in binding free energy (Betel et al, 2010;Liu et al, 2012). In addition, some studies investigated the effects of SNPs according to the secondary structures of the miRNA binding sites by using RNAfold (Hariharan et al, 2009).…”

Not all good things come in big packages

“…This has raised an interest in the connection between single nucleotide polymorphisms (SNPs) and human disease [12]. SNPs not only elicit an impact on protein functions but are also conducive to impaired interactions between miRNAs and their targets [25]. SanGiovanni et al [26] investigate the impact of SNPs on miRNA regulation in the context of age-related macular degeneration.…”