miRNA:miRNA Interactions: A Novel Mode of miRNA Regulation and Its Effect On Disease.

MicroRNAs (miRNAs) are known for their role in the post-transcriptional regulation of messenger RNA (mRNA). However, recent evidence has shown that miRNAs are capable of regulating non-coding RNAs, including miRNAs, in what is known as miRNA:miRNA interactions. There are three main models for the interplay between miRNAs. These involve direct interaction between two miRNAs, either in their mature or primary form, the subsequent changes in miRNA expression due to miRNA-directed transcriptional changes, and the cell-wide impact on miRNA and mRNA levels as a result of miRNA manipulation. Networks of mRNA and miRNA regulatory connections are invaluable to the discovery of miRNA:miRNA pathways, but this cannot be applied without consideration of the specific cell type or condition.In this chapter, we discuss what is understood about miRNA:miRNA interactions, their mechanisms and consequences in disease biology, and suggest further avenues of investigation based on current gaps in the literature and in our understanding of miRNA biology. We also address the pitfalls in contemporary methods relating to the identification of miRNA:miRNA interactions. Future work in this area may ultimately change the definitional role of miRNAs, and have far-reaching impacts on therapeutic and diagnostic developments.