Computational Analysis of miRNA and Target mRNA Interactions: Combined Effects of The Quantity and Quality of Their Binding Sites / 生物化学与生物物理进展

ABSTRACT

MicroRNAs (miRNAs) act by binding to complementary sites on target messenger RNA (mRNA) to induce mRNA degradation and/or translational repression. To investigate the influence of miRNAs at transcript levels, two human miRNAs (miR-1 and miR-124) were transfected into HeLa cells and microarrays used to examine changes in the mRNA profile showed that many genes were downregulated and that the fold decreases in levels of these target mRNAs differed remarkably. Features depicting interactions between miRNAs and their respective target mRNAs, such as the number of putative binding sites, the strength of complementary matches and the degree of stabilization of the binding duplex, were extracted and analyzed. It was found that, for a given target mRNA, both the quality and quantity of miRNA binding sites significantly affected its degree of destabilization. To delineate these types of interactions, a simple statistical model was proposed, which considers the combined effects of both the quality and quantity of miRNA binding sites on the degradation levels of target mRNAs. The analysis provides insights into how any animal miRNA might interact with its target mRNA. It will help us in designing more accurate methods for predicting miRNA targets and should improve understanding of the origins of miRNAs.