Gene silencing

Abstract

Early experiments in which a gene was transferred from one species to another were very exciting but were often disappointing in that the gene expression seen in the first generation was not carried through to subsequent generations. It also became clear that this silencing was not a result of incomplete or erroneous translation. A major breakthrough was the work of Dougherty and colleagues who showed that aberrant RNA led to lengthy but often incomplete or rearranged RNA species. By 1998, it was recognized both in animal and plant systems that rearrangements of the transgene that allowed anti-parallel RNA strands to be generated stimulated a templated degradation system (RISC complex) that includes specific small RNAs together with Argonaute proteins and Dicer-like proteins that cleave the targeted RNA into characteristic 21-25 nt degradation products. In addition to induction by anti-parallel RNAs, RNAi degradation systems can be induced by virus replication intermediates as in natural host defense mechanisms. By 2001, another kind of small RNA involved in regulation of gene expression was discovered and termed microRNA. These endogenous ∼21 nt small RNAs play several roles in gene regulatory networks and often target other regulatory genes. Artificial small RNAs can also be designed to inactivate target genes to generate the mutant phenotypes which are useful for crop improvement. Thus, whereas the instability of transgene expression is seen as an undesirable feature, correctly used, similar strategies are proving powerful in debilitating many pathogens for which no protection has been available from classical sources. © 2009 Springer Science+Business Media B.V.