RNA Interference and Antisense Mediated Gene Silencing

Abstract

Gene silencing by RNA interference (RNAi) and by antisense RNA are powerful tools to interfere with the expression of eukryotic genes. Since the first description of RNAi in 1998, antisense-mediated gene silencing has been considered to have essentially the same mechanism as gene silencing by RNAi. However, while substantial effort has been made to dissect the RNAi pathway, the cellular machinery that is responsible for posttranscriptional regulation by antisense RNA is rather poorly defined and direct comparisons between the RNAi and antisense experiments are rare. Even though similarities are very likely, recent data suggest that in addition to the expected overlaps in the pathways, there are also mechanistic differences and different requirements for specific gene products. We will summarize the current state of knowledge of the antisense RNA and RNAi mechanisms and address some of the open questions in the field. We will further provide some evidence suggesting that gene silencing by antisense RNA and by RNAi represent related but not identical mechanisms. A model to explain the partially overlapping pathways will be presented and may contribute to the further understanding of posttranscriptional gene regulation.