Chapter 2 - Harnessing RNAi to Silence Viral Gene Expression

Abstract

Since discovery of the RNA interference (RNAi) pathway, there has been rapid progress in research aimed at harnessing this gene silencing mechanism for antiviral therapeutic application. Micro RNAs (miRs) are the prototype natural activators of RNAi. Their maturation entails a regulated stepwise process during which transcripts with hairpin motifs within primary miRs (pri-miRs) are cleaved by the nuclear microprocessor complex to generate precursor miRs (pre-miRs). pre-miRs are exported to the cytoplasm before further processing by Dicer, an RNase III, to generate the mature miR comprising a short duplex RNA sequence. One of the strands is selected for incorporation into the RNA induced silencing complex (RISC), where it naturally serves as a guide to direct translational suppression of mRNA targets. Cellular and viral mechanisms operate to control miR maturation and thereby modulate gene silencing by these short RNA sequences.