Multiple Genetic Polymorphisms within microRNA Targets and Homologous microRNA-Binding Sites: Two More Factors Influencing microRNA-Mediated Regulation of Gene Expression

Abstract

miRNA-mRNA interaction depends on multiple factors such as 3’UTR isoforms, the cell and tissue-specific expression levels of RNA-binding proteins, the sequence context around the mRNA target site, and other mechanisms. Genetic polymorphisms within miRNAs and their target sites appear to be among the most important ones because they influence the mode and outcome of miRNA-mRNA interaction universally and irreversibly. SNP disruption of miRNAs and their binding sites, as well as conformational changes preventing the access of the miRNA to its target site, are adopted as the most credible mechanistic explanations of SNP-mediated effects. The occurrence of multiple SNPs within the same miRNA-binding site implies their combinatorial mode of action. The presence of the repetitive (homologous) binding sites for the same miRNA on its mRNA target may both enhance the miRNA targeting and provide for the backup target site instead of the one disrupted by SNP, thus rescuing the miRNA functionality. While being underexplored, the multiple genetic polymorphisms within the miRNA-binding sites, as well as homologous miRNA-binding sites, may be considered as additional factors influencing miRNA-mediated regulation of gene expression.