Conclusion
The diversity of miRNA activity in the cellular system is noteworthy, and hard to comprehend by just performing high-quality experiments. In recent years, investigations using combined high throughput experimental techniques and computational methods for finding miRNA targets and miRNA activity provided a detailed understanding of miRNA-mediated gene regulation.52–56 However, in gene regulatory networks, where miRNAs themselves are regulated by other proteins and are part of complex dynamics, network-specific analyses are required. For example; multiple mRNAs compete for a miRNA, or multiple miRNAs targeting a single mRNA. It is worthwhile to look into the target repression dynamics when multiple miRNAs of varying inhibition efficiency act on the same target. A recent study in C. elegans for Lin 4 protein show that the location of binding sites can favor different modes of inhibition like mRNA decay when miRNA binds to 3’UTR and translation repression for 5’UTR binding.118Single-cell studies have provided more insights into the dynamics of miRNA repression kinetics and turned out to be the major determinants of miRNA activity.53,54 miRNAs also upregulate target expression in the presence of certain RNA binding proteins and environment conditions.15,106,107 Even though few models have proposed a possible mechanism for miRNA mediated target upregulation,84,105 their predictions have to be validated by experiments.
More computational algorithms and mathematical models have to be developed to investigate the interaction between RNA binding proteins and miRNAs and how such interactions affect the miRNA function. Especially in the context of noise buffering by miRNAs, understanding complex networks involving miRNAs and the effect of competing RNA’s in miRNA regulation, mathematical and computational models will play a critical role in understanding the miRNA dynamics. A system biology approach will be crucial to decipher the actual mode of action of miRNA in a network-specific manner. Getting such a quantitative understanding of miRNA-mediated gene regulation in signaling pathways involved in cancer and other related diseases will enable us to develop novel therapeutic strategies for the same.