Computational methods to identify miRNA targets

Abstract

MicroRNAs (miRNAs) are short RNA molecules that regulate the post-transcriptional expression of their target genes. This regulation may take the form of stable translational or degradation of the target transcript, although the mechanisms governing the outcome of miRNA-mediated regulation remain largely unknown. While it is becoming clear that miRNAs are core components of gene regulatory networks, elucidating precise roles for each miRNA within these networks will require an accurate means of identifying target genes and assessing the impact of miRNAs on individual targets. Numerous computational methods for predicting targets are currently available. These methods vary widely in their emphasis, accuracy, and ease of use for researchers. This review will focus on a comparison of the available computational methods in animals, with an emphasis on approaches that are informed by experimental analysis of microRNA:target complexes.

Figure 1. Parameters of functional microRNA Targets

Shown in panel (A) is a cartoon of microRNAs and RNA binding proteins interacting with a target mRNA. The parameters listed here have experimental motivation for their importance in functional microRNA targets. These include (1) parameters of the individual binding sites detailed in panel B, (2) the presence of cooperating miRNAs, and (3) the presence of interacting proteins. Panel (B) shows a detailed inset of a particular miRNA binding site incuding: (1a) the seed region, (1b) the thermostability of the duplex (MFE), and (1c) the structural accessibility of regions around the miRNA binding site. Parameters not shown in this figure include conservation of binding sites and the relative expression level of miRNA to target mRNA.