The most useful discoveries in the paper involved the assignment of functions to specific RNA silencing factors, especially those involved in the transcriptional silencing pathway. The mutant series we developed and the approaches used to link RNA silencing functions to heterochromatin formation have been used by many other groups. Some of the key methodologies were developed by our collaborators, Steve Jacobson and his group at UCLA.

This work is a small part of a much larger revolution in how we understand genetics and how genes are regulated. RNA silencing—or RNA interference (RNAi)—processes that are described in this paper occur in most complex organisms such as plants, flies, and people. This means that the RNAi mechanism has been around since before plants diverged from animals in evolution. We used the plant Arabidopsis thaliana as a productive model to explore some of the basic mechanisms that control RNAi. Recent research in animals shows that deviations in RNAi-related processes, involving small RNAs called microRNAs, likely play a role in various pathologies. Additionally, small RNAs that function in RNAi are being developed as drugs in many labs and companies. So, understanding the silencing pathways and mechanisms, we believe, may have important benefits in the future.

This lab became involved in RNA silencing back in the mid-1990s, when it was only poorly understood and before anyone was aware of how widespread the process occurs in complex organisms. We were one of several labs exploring how RNA silencing functioned as an antiviral defense response in plants, and how viruses counteracted the silencing response to establish systemic infections. This led to the discovery, along with a few other labs, of RNA silencing suppressor proteins encoded by viruses. We reasoned that if the silencing response was effective against viruses, perhaps there were endogenous RNA silencing pathways regulating cellular genes. This led to the identification of endogenous siRNAs resulting from silencing of transposons, retroelements, and other repeated sequences, as well as some of the initially recognized plant microRNAs. Most of our work since then has focused on understanding plant silencing pathways and how the system evolved to engage so many different cellular and defense processes.

There actually are some social and political implications of this work, but not how you might guess. This was one of the early papers published in PLoS Biology, an open access journal founded on principles that differed considerably from many or most other scientific journals. We believed in the philosophy behind the PLoS journals—open and immediate access to all scientists and anyone else. We also believed in the way PLoS Biology was organized, and felt it would rapidly emerge as one of the major biological journals. We are very pleased that this paper has received the citations it has, in part because, in a small way, it validates the open access publishing model.