Catalog of MicroRNA Seed Polymorphisms in Vertebrates

Abstract

MicroRNAs (miRNAs) are a class of non-coding RNA that plays an important role in posttranscriptional regulation of mRNA. Evidence has shown that miRNA gene variability might interfere with its function resulting in phenotypic variation and disease susceptibility. A major role in miRNA target recognition is ascribed to complementarity with the miRNA seed region that can be affected by polymorphisms. In the present study, we developed an online tool for the detection of miRNA polymorphisms (miRNA SNiPer) in vertebrates (http://www.integratomics-time.com/miRNA-SNiPer) and generated a catalog of miRNA seed region polymorphisms (miR-seed-SNPs) consisting of 149 SNPs in six species. Although a majority of detected polymorphisms were due to point mutations, two consecutive nucleotide substitutions (double nucleotide polymorphisms, DNPs) were also identified in nine miRNAs. We determined that miR-SNPs are frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits. To test this further, we performed an association analysis between the mmu-miR-717 seed SNP rs30372501, which is polymorphic in a large number of standard inbred strains, and all phenotypic traits in these strains deposited in the Mouse Phenome Database. Analysis showed a significant association between the mmu-miR-717 seed SNP and a diverse array of traits including behavior, blood-clinical chemistry, body weight size and growth, and immune system suggesting that seed SNPs can indeed have major pleiotropic effects. The bioinformatics analyses, data and tools developed in the present study can serve researchers as a starting point in testing more targeted hypotheses and designing experiments using optimal species or strains for further mechanistic studies.

SNP in pre-miR-1666 decreases mature miRNA expression and is associated with chicken performance

“…For instance, Jazdzewski et al reported that an SNP in pre-miR-146a affected the miRNA expression, promoted the genetic predisposition to papillary thyroid carcinoma, and played a role in the tumorigenesis through somatic mutation (Jazdzewski et al 2008). Zorc et al determined that miR-SNPs were frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits (Iwai and Naraba 2005;Duan et al 2007;Zorc et al 2012).…”

“…Becaue polymorphisms can change the stem-loop structure, polymorphisms in miRNA genes could potentially alter various biological processes by influencing the processing and (or) target selection of miRNAs (Iwai and Naraba 2005;Duan et al 2007;Zorc et al 2012). It was shown that a SNP in the pri-miR-126 significantly blocked the processing of pri-miRNA to mature miRNA, as well as reduced miRNA-mediated translational suppression (Harnprasopwat et al 2010).…”

“…This mutation is located at the lower stem of miRNA, which is critical to determine Drosha and Dicer cleavage (Zorc et al 2012;Auyeung et al 2013;Ma et al 2013). This study aims at investigating whether the SNP located in the lower stem of miRNA secondary structure could affect the biological processes of miRNA, and further analyzing the biological function of this SNP in miR-1666.…”

Identifying a Polymorphic ‘Switch’ That Influences miRNAs' Regulation of a Myasthenia Gravis Risk Pathway

“…The miRSNPs within miRNAs were obtained from Patrocles (2013 July) [28], miRNA-SNiPer (version 3.9) [34], and miRNASNP (release 1.0) [29]; For both kinds of miRSNPs, we focused on the miRSNPs of interest being predicted by at least two databases, and all of these miRSNPs may potentially disrupt existing interactions between miRNA and mRNA.…”

Assessment of correlation between pre-miRNA-1757 polymorphism and chicken performance traits

“…MI0007499) was designed according to the public chicken genome sequence (NR_035258.1). The PCR product was purified using a kit (Tiangen Biotech Co., Ltd., Beijing, China), and sequenced by Sangon Biotech Co., Ltd. (Shanghai, China) to scan SNPs in the miR-1757 precursor region (Zorc et al, 2012).…”