MicroRNA (miRNA) are an abundant class of short, non-coding RNAs that were discovered just over a decade ago, and are now understood to be important regulators of gene expression. Hundreds of miRNAs are encoded in the human genome, and each cell type and cell state has been reported to express a unique profile of miRNA. miRNAs regulate gene expression by guiding Argonaute proteins to specific sequences in transcripts. In mammals, the vast majority of natural target sites are not perfectly complementary, and regulation occurs through a nonslicing mechanism in which the miRNA-Ago complex inhibits translation and/or promotes destabilization of the transcript. Because miRNAs need only as few as 7 nucleotides of complementarity to bind to their target, thousands of different genes can be subject to regulation by a single miRNA or miRNA family. Although much has been learned about miRNA biology, fundamental questions remain, and the function of many miRNAs is still unknown.
Our lab is trying to understand the relationship between miRNA concentration and target regulation. We have shown that many miRNAs that are detectably expressed in a cell have little to no activity, as measured using a sensitive reporter assay. In some cases this appears to be because the miRNA’s abundance is below a threshold concentration. However, there also appears to be post-transcriptional mechanisms that are controlling miRNA activity independent of the miRNA’s concentration. We are trying to identify these mechanisms with the hope that this will lead to a better understanding of miRNA biology and provide a means to modulate the activity of specific miRNAs.