In the McManus lab, one of our projects has been focused on the post-transcriptional regulation of miRNAs. In particular, we are intent on determining the regulation of miRNA expression and stability. There are numerous mechanisms cells take to maintain the steady state level of small RNAs and we are uncovering these pathways one step at a time.
Studies of miRNAs in developmental settings have demonstrated that miRNA expression is extensively regulated at the temporal and spatial levels. Despite these findings, there is very little information on the mechanisms of how miRNA expression is regulated at the transcriptional and post-transcriptional levels. This is partly because the field is still quite new and also because of the challenging nature of monitoring the turnover of such small RNAs.
For example, it will be very interesting to determine if miRNA half-lives are on the order of seconds, minutes, days or if some miRNAs can persist for the life-time of the cell (there is certainly much speculation that miRNAs may have long half-lives). This data may be particular useful for not only understanding miRNA function or dysfunction in the cell (such as in development or synaptic plasticity), but also in the development of small RNA therapeutics.
It will be important to delineate factors involved in processes such as half-life. There is much synergism in our group since library efforts aimed at screening microRNA activity in cells will likely help to uncover genes that participate in the post-transcriptional regulation of small RNA stability.