A robust model for quantitative prediction of the silencing efficacy of wild-type and A-to-I edited miRNAs

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in the regulation of gene function by a mechanism known as RNA silencing. In a previous study, we revealed that miRNA-mediated silencing efficacy is correlated with the combinatorial thermodynamic properties of the miRNA seed–target mRNA duplex and the 5´-terminus of the miRNA duplex, which can be predicted using ‘miScore’. In this study, a robust refined-miScore was developed by integrating the thermodynamic properties of various miRNA secondary structures and the latest thermodynamic parameters of wobble base-pairing, including newly established parameters for I:C base pairing. Through repeated random sampling and machine learning, refined-miScore models calculated with either melting temperature (Tm) or free energy change (ΔG) values were successfully built and validated in both wild-type and adenosine-to-inosine edited miRNAs. In addition to the previously reported contribution of the seed–target duplex and 5´-terminus region, the refined-miScore suggests that the central and 3´-terminus regions of the miRNA duplex also play a role in the thermodynamic regulation of miRNA-mediated silencing efficacy.