Redefining MicroRNA Targets

Animal microRNAs (miRNAs) guide proteins to repress the translation of target mRNAs via imperfect base pairing between the miRNA and the target. Computational analyses suggest that each miRNA regulates tens or hundreds of targets [1, 2], yet genetic studies usually show that the repression of a few targets plays a physiological role [3-5]. The extent of miRNA-mediated repression (which rarely exceeds 2-fold [1, 2]) is also surprisingly lower than most well-tolerated, intrinsic variations in gene expression [6, 7]. Although miRNA targets are well conserved among closely related species, they differ greatly between more distant animals [8]. The prevailing view is that miRNAs tune expression of most of their targets [1, 2]. Here, I propose an alternative hypothesis that could resolve these three paradoxes: many computationally identified miRNA targets may actually be competitive inhibitors of miRNA function, preventing miRNAs from binding their authentic targets by sequestering them. Depending on the prevalence of this type of miRNA:mRNA interaction, this new conception of miRNA regulation could have profound implications on our assumptions about miRNA function.