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.