The article by Brennecke et al. (2005) systematically evaluates the minimal requirements for functional miRNA-target duplexes in vivo and identifies two broad categories of target sites: 5′ dominant sites and 3′ compensatory sites. 5′ dominant sites have sufficient complementarity to the miRNA 5′ end to function with little or no support from pairing to the miRNA 3′ end, while 3′ compensatory sites require strong 3′ pairing for function. The study provides evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that the 3′ ends of miRNAs are key determinants of target specificity within miRNA families. The authors also discuss the role of G:U base-pairs and bulges in the seed region, and the functional categories of target sites, including canonical sites, seed sites, and 3′ compensatory sites. They conclude that the majority of miRNA target sites lack substantial pairing in the 3′ end, and estimate that there are over 80 5′ dominant sites and 20 or fewer 3′ compensatory sites per miRNA in the Drosophila genome, suggesting that a large fraction of genes are regulated by miRNAs.The article by Brennecke et al. (2005) systematically evaluates the minimal requirements for functional miRNA-target duplexes in vivo and identifies two broad categories of target sites: 5′ dominant sites and 3′ compensatory sites. 5′ dominant sites have sufficient complementarity to the miRNA 5′ end to function with little or no support from pairing to the miRNA 3′ end, while 3′ compensatory sites require strong 3′ pairing for function. The study provides evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that the 3′ ends of miRNAs are key determinants of target specificity within miRNA families. The authors also discuss the role of G:U base-pairs and bulges in the seed region, and the functional categories of target sites, including canonical sites, seed sites, and 3′ compensatory sites. They conclude that the majority of miRNA target sites lack substantial pairing in the 3′ end, and estimate that there are over 80 5′ dominant sites and 20 or fewer 3′ compensatory sites per miRNA in the Drosophila genome, suggesting that a large fraction of genes are regulated by miRNAs.