Got target? Computational methods for microRNA target prediction and their extension

Abstract

MicroRNAs (miRNAs) are a class of small RNAs of 19-23 nucleotides that regulate gene expression through target mRNA degradation or translational gene silencing. The miRNAs are reported to be involved in many biological processes, and the discovery of miRNAs has been provided great impacts on computational biology as well as traditional biology. Most miRNA-associated computational methods comprise the prediction of miRNA genes and their targets, and increasing numbers of computational algorithms and web-based resources are being developed to fulfill the need of scientists performing miRNA research. Here we summarize the rules to predict miRNA targets and introduce some computational algorithms that have been developed for miRNA target prediction and the application of the methods. In addition, the issue of target gene validation in an experimental way will be discussed.

Figure 1

MicroRNA biogenesis and function in animal cells (Lodish et al., 2008). miRNAs are transcribed as long primary transcripts (pri-miRNAs) in the nucleus. The pri-miRNAs are then processed by the RNase III-type Drosha, yielding pre-miRNAs of ~70 nucleotide (nt). Subsequently, the pre-miRNAs are exported to the cytoplasm by exportin-5, and further cleaved into ~21 to 22 nucleotide miRNA duplex by another RNase III enzyme Dicer. The less stable strand of the miRNA duplex is then incorporated into a multiple protein nuclease complex, the RISC, and regulates protein expression.

Figure 2

Approximate secondary structures of the three main types of target site duplex. (A) Canonical sites have perfect base paring in seed region, a bulge in the middle and extensive base pairing in the 3' end of the miRNA. (B) Dominant seed sites form perfect complementarity in the seed, but poor complementarity in the 3' end of the miRNA. (C) Compensatory sites have a mismatch or G:U wobble in the seed region, but have extensive base pairing to the 3' end of the miRNA (Maziere and Enright, 2007).