%0 Journal Article
%T RNAi in the regulation of mammalian viral infections
%A Kuan-Teh Jeang
%J BMC Biology
%D 2012
%I BioMed Central
%R 10.1186/1741-7007-10-58
%X RNA interference (RNAi) is a process in which small non-coding RNAs (of endogenous or exogenous origin) are incorporated into a multi-protein RNA-induced silencing complex (RISC) in cells to silence the expression of a sequence-homologous target RNA [1]. Three major types of small non-coding RNAs function as RNAi: the piRNAs (PIWI-interacting RNAs), miRNAs (microRNAs), and siRNAs (small interfering RNAs). piRNAs and miRNAs are endogenous, small non-coding RNAs transcribed from cellular loci and then processed to generate fragments that engage with the downstream silencing machinery. Until recently, siRNAs were thought to be exclusively processed from the exogenous RNA of pathogens (for example, viruses) that infect the cell, but that view changed with the discovery of abundantly expressed endogenous siRNAs (endo-siRNAs) in animal cells [2,3]. Currently, mammals are known to have hundreds of thousands of different piRNAs, produced from gene clusters of repetitive elements, and more than 1,000 different miRNAs; the number of endo-siRNAs still needs to be fully clarified.Simplified representations of the different RISC complexes are shown schematically in Figure 1. miRNA biogenesis requires the RNAse III proteins Drosha and Dicer, while siRNA processing depends solely on Dicer, and the nuclease(s) required for piRNA processing remain(s) unidentified [4]. Short double-stranded RNAs (dsRNAs) are bound to form the miRNA- and siRNA-RISC complex while the biogenesis of the piRNA-RISC can arise from either a single-stranded precursor RNA or through a 'ping-pong' mechanism [1]. A major constituent of the miRNA-RISC and siRNA-RISC complexes is the AGO protein; the parallel constituent in piRNA-RISC is the PIWI protein. In the RISC complex, a guide RNA strand is retained that captures target mRNA through complete or incomplete sequence complementarity. The RISC complex then may either inhibit translation of the mRNA or, through the so-called slicer activity of the AGO and PIWI
%U http://www.biomedcentral.com/1741-7007/10/58