Our structure and the discovery that the PAZ domain binds to the 3' ends of siRNAs are important elements in understanding the mechanism of RNAi. When we began our research there had been remarkable progress in unraveling the components of the RNAi machinery, but not how they all fit together. This was the first step—after which we took a few other important ones—to achieve a real molecular understanding of this very important pathway. Understanding the mechanism of RNAi in this kind of detail is a key for improving the technology as a tool for gene silencing and also as a therapeutic.

RNA interference (RNAi) has emerged as a widespread biological regulatory mechanism, a powerful tool for both basic and applied research, and as a therapeutic strategy of enormous potential. In organisms from fungi and flies to plants and humans, RNAi plays an essential, multifaceted role in controlling gene expression. One of the best-studied RNAi mechanisms is the quashing of gene expression through the cleavage and destruction of templates for protein synthesis called "messenger RNA," or mRNA. Two of the main players in this process are proteins called Dicer and Argonaute; both have a characteristic region or domain called the PAZ domain that is present only in these types of RNAi proteins. We provided the first detailed picture, at near-atomic resolution, of the shape or structure of this domain. This is the first glimpse into a molecular structure of an important component in the RNAi pathway. We also showed how this domain binds (holds on) to one of the ends of the trigger of this process—the siRNA. PAZ is shaped like a right-handed baseball glove (see illustration) and the end of the siRNA would fit in the region between the thumb, fingers and palm of the glove.