MicroRNAs coordinately regulate protein complexes

In animals, microRNAs (miRNAs) regulate the protein synthesis of their target messenger RNAs (mRNAs) by either translational repression or deadenylation. miRNAs are frequently found to be coexpressed in different tissues and cell types, while some form polycistronic clusters on genomes. Interactions between targets of co-expressed miRNAs (including miRNA clusters) have not yet been systematically investigated. Here we integrated information from predicted and experimentally verified miRNA targets, to characterize protein complex networks regulated by human miRNAs. We found striking evidence that individual miRNAs or co-expressed miRNAs frequently target several components of protein complexes - indicating a coordinate posttranscriptional regulation of protein complexes by miRNAs. We experimentally verified that the miR-141-200c cluster targets different components of the CtBP/ZEB complex, suggesting a potential orchestrated regulation in epithelial to mesenchymal transition. Thus, our results should provide a sound basis for designing experiments to study miRNA function at a systems level.