A robust model for quantitative prediction of the silencing efficacy of wild-type and A-to-I edited miRNAs. Issue 2 (1st February 2020)

• Record Type: Journal Article
• Authors: Tian, Shen; Terai, Goro; Kobayashi, Yoshiaki; Kimura, Yasuaki; Abe, Hiroshi; Asai, Kiyoshi; Ui-Tei, Kumiko
• Is Part Of: RNA biology. Volume 17:Issue 2(2020)
• Page Start: 264
• Page End: 280
• Publication Date: 2020-02-01
• Subjects: miRNA -- silencing efficacy -- thermodynamics -- RNA editing -- machine learning -- miScore; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2019.1678364
• Languages: English
• ISSNs: 1547-6286

Abstract

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.