Principles of MicroRNA-target recognition

MicroRNAs ( miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically evaluate the minimal requirements for functional miRNA - target duplexes in vivo and distinguish classes of target sites with different functional properties. Target sites can be grouped into two broad categories. 59 dominant sites have sufficient complementarity to the miRNA 59 end to function with little or no support from pairing to the miRNA 39 end. Indeed, sites with 39 pairing below the random noise level are functional given a strong 59 end. In contrast, 39 compensatory sites have insufficient 59 pairing and require strong 39 pairing for function. We present examples and genome-wide statistical support to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 39 ends are key determinants of target specificity within miRNA families.