Accessibility of microRNA binding sites in metastable RNA secondary structures in the presence of SNPs

Abstract

We study microRNA (miRNA) bindings to metastable RNA secondary structures close to minimum free energy conformations in the context of single nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) concentration levels, i.e. whether features of miRNA bindings to metastable conformations could provide additional information supporting the differences in expression levels of the two sequences defined by a SNP. In our study, the instances [mRNA/3'UTR; SNP; miRNA] were selected based on strong expression level analyses, SNP locations within binding regions and the computationally feasible identification of metastable conformations. We identified 14 basic cases [mRNA; SNP; miRNA] of 3' UTR-lengths ranging from 124 up to 1078 nt reported in recent literature, and we analyzed the number, structure and miRNA binding to metastable conformations within an energy offset above mfe conformations. For each of the 14 instances, the miRNA binding characteristics are determined by the corresponding STarMir output. Among the different parameters we introduced and analyzed, we found that three of them, related to the average depth and average opening energy of metastable conformations, may provide supporting information for a stronger separation between miRNA bindings to the two alleles defined by a given SNP. At http://kks.inf.kcl.ac.uk/MSbind.html the MSbind tool is available for calculating features of metastable conformations determined by putative miRNA binding sites.