Planting the Seeds of a New Paradigm

Although the word ‘revolution’ should not be used lightly in science, there is no other way to describe the recent explosion in our awareness and understanding of RNAmediated gene silencing pathways. The central player in RNA-mediated gene silencing is a double-stranded RNA (dsRNA) that is chopped into tiny RNAs by the enzyme Dicer. The tiny RNAs associate with various silencing effector complexes and attach to homologous target sequences (RNA or DNA) by basepairing. Depending on the protein composition of the effector complex and the nature of the target sequence, the outcome can be either mRNA degradation, translational repression, or genome modifi cation, all of which silence gene expression (Figure 1). Present in plants, animals, and many fungi, RNA-mediated gene silencing pathways have essential roles in development, chromosome structure, and virus resistance. Although the mechanistic details are still under investigation, RNA-mediated silencing has already provided a powerful tool for studying gene function and spawned a fl edgling industry that aims to develop novel RNA-based therapeutics to treat human diseases (Robinson 2004). Many biologists fi rst learned of RNA-mediated gene silencing in 1998 following the discovery, in the nematode worm Caenorhabditis elegans (Fire et al. 1998), of a process called RNA interference (RNAi), in which dsRNA triggers sequence-specifi c mRNA degradation. The roots of RNA-mediated silencing, however, can be traced back 15 years, when a handful of botanical labs stumbled across strange cases of gene silencing in transgenic plants. To highlight the many seminal contributions of plant scientists to the fi eld, we offer here a personal perspective on the origins and history of RNA-mediated gene silencing in plants.