14 - The RNAhybrid approach to microRNA target prediction

Summary

Introduction

MicroRNAs (miRNAs) are 19–24 nt long RNAs that post-transcriptionally regulate their target genes. The regulation is effected by binding of the RISC-incorporated miRNA to the target mRNA. Upon near-perfect hybridization, the target mRNA is cleaved and subsequently degraded. Less strong hybridizations lead to translational repression of the mRNA or to its degradation. Besides the elucidation of mechanistic aspects of the miRNA pathway, the reconstruction of the miRNA regulatory network is of great interest. A fundamental part in the reconstruction process is the knowledge of miRNA targets. Since reverse-genetic approaches are limited by their time and cost-intensiveness, a reliable prediction of miRNA targets is indispensable. Indeed, while the total number of targeted genes is estimated to be one third of the whole human gene complement, 10 000 genes (Lewis et al., 2005), the current number of experimentally validated targets, according to the Diana TarBase (Sethupathy et al., 2006; see also Chapter 13 in this book), is 55 (at the time of writing). A number of prediction methods have contributed considerably to the generation of interesting hypotheses about possible animal miRNA/target relationships (John et al., 2004; Kiriakidou et al., 2004; Rehmsmeier et al., 2004; Brennecke et al., 2005; Lall et al., 2006).

RNAhybrid is a method that offers a database of target predictions, a download version, and an easy-to-use web-interface for online target predictions. At the same time, RNAhybrid allows the user broad control of the search. One area of control is the structural requirements of a miRNA/target interaction.