Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer

Abstract

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important regulators of mRNA stability and translation in eukaryotic cells; however, the complex interplay between these systems is only now coming to light. RBPs and miRNAs regulate a unique set of targets in either a positive or negative manner and their regulation is mainly opposed to each other on overlapping targets. In some cases, the levels of RBPs or miRNAs regulate the cellular levels of one another and decreased levels of either results in changes in translation of their targets. There is growing evidence that these regulatory circuits are crucial in the development and progression of cancer; however, the rules underlying synergism and antagonism between miRNAs and RNA-binding proteins remain unclear. Synthetic biology seeks to develop artificial systems to better understand their natural counterparts and to develop new, useful technologies for manipulation of gene expression at the RNA level. The recent development of artificial RNA-binding proteins promises to enable a much greater understanding of the importance of the functional interactions between RNA-binding proteins and miRNAs, as well as enabling their manipulation for therapeutic purposes.

Keywords: Designer RNA-binding proteins; PUF domain; Pentatricopeptide repeat; RNA interference; RNA–protein interactions; Synthetic biology; miRNA.

Fig. 1

Schematic overview of the miRNA biogenesis pathway

Fig. 2

Schematic representation of the design of a novel miRNA binding protein [17]

Fig. 3

Schematic representations of the structures and binding codes of PUF (a) and PPR proteins (b)