MicroRNAs repress translation of m⁷Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation

The past decade has witnessed a veritable explosion in research into identifying the microRNA (miRNA) repertoires of various organisms and predicting the mRNA targets of these numerous miRNAs. By contrast, until quite recently, relatively little work had been done on investigating the mechanisms by which miRNAs control gene expression, which is the topic of this Perspective. We will concentrate primarily on mechanisms in vertebrates, drawing on Drosophila and Caenorhabditis elegans data where relevant but largely omitting plant miRNAs, as these seem sufficiently different in terms of mechanisms of action to make extrapolation between plant and vertebrate systems problematic. Although the current controversies over the exact mechanism of miRNA-mediated regulation of gene expression have been discussed in a number of recent reviews (Jackson and Standart 2007; Nilsen 2007; Pillai et al. 2007), what makes this additional article particularly timely are three reports of successful recapitulation of repression in cell-free systems, notably the results of Wakiyama et al. (2007) published in the previous issue, which is arguably the system that is the closest parallel to what is believed to occur in intact cells. Before discussing this article, however, we will first provide some background and will review the current (rather controversial) state of knowledge derived from transfection assays and other work with intact cells.