MicroRNA-mediated regulation of gene expression is affected by disease-associated SNPs within the 3′-UTR via altered RNA structure

2012 
Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) or their target sites (miR-SNPs) within the 3′-UTR of mRNAs are increasingly thought to play a major role in pathological dysregulation of gene expression. Here, we studied the functional role of miR-SNPs on miRNA-mediated post-transcriptional regulation of gene expression. First, analyses were performed on a SNP located in the miR-155 target site within the 3′-UTR of the Angiotensin II type 1 receptor (AGTR1; rs5186, A > C) mRNA. Second, a SNP in the 3′-UTR of the muscle RAS oncogene homolog (MRAS; rs9818870, C > T) mRNA was studied which is located outside of binding sites of miR-195 and miR-135. Using these SNPs we investigated their effects on local RNA structure, on local structural accessibility and on functional miRNA binding, respectively. Systematic computational RNA folding analyses of the allelic mRNAs in either case predicted significant changes of local RNA structure in the vicinity of the cognate miRNA binding sites. Consistently, ...
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