An underlying theme in the regulation of miRNA biogenesis at the Drosha processing step seems to be that regulatory proteins selectively alter the expression of certain subsets of miRNAs. This is not entirely surprising, as the cellular functions of miRNAs are diverse, and global up-regulation or down-regulation of all miRNAs might cause havoc on cellular systems. The miRNA subsets whose expression are altered by the regulatory proteins discussed above seem to be in line with the traditionally accepted roles for those proteins. As more and more regulatory proteins are discovered for all steps of miRNA production and processing, it is most likely that this theme will be extended. The activation of Smad proteins is associated with cell growth and transformation, and the miRNAs that are regulated by Smads are associated with similar effects. On the other hand, expression and activation of p53 is a well known mechanism of cell cycle arrest and apoptosis, and its downstream miRNAs can be effectors of the same pathways. While Ars2 is not a very well-studied protein and its detailed function remains to be fully elucidated, recent research shows that it is involved in cell proliferation. Likewise, the miRNAs that Ars2 has been shown to regulate are involved in similar cellular functions. Additional research should be done to delineate exactly which miRNAs are in each regulated subset. This information would be useful for determining if therapeutic intervention of proteins, such as Ars2, would be a fruitful endeavor.
One exception to the theme is the observed activation of miRNA biogenesis by cell-to-cell contacts. This effect appears to be global (with few exceptions), including the expression of miRNA that have historically opposite effects. Cellular signaling that occurs during quiescence is highly complex, and the study by Hwang et al. now places miRNA expression into the mix [69
As the study of miRNA biogenesis continues, it is apparent that more proteins will be discovered to play regulatory roles at various processing steps. It will be important to determine whether or not these proteins or processing pathways are legitimate targets for therapeutic intervention. It is becoming increasingly clear that subsets of miRNA play important roles in multiple disease states. If there are master regulators of expression of these subsets, they could be potential targets for intervention and may be critical for the alleviation of symptoms or reversal of disease.