Greg Hannon, Cold Spring Harbor Laboratory,
In plants animals and some fungi, double stranded RNAs induce a sequence specific gene silencing response known as RNA interference or RNAi. This system relies on signature small RNAs of about 22 nucleotides in length to direct an RNP effector complex, RISC, to its targets. These targets can be silenced through any of several different effector mechanisms, including RNA cleavage, repression of protein synthesis and inhibition of transcription. My laboratory uses a variety of model systems, ranging from plants to Drosophila to mammals to study interference process from multiple perspectives. We investigate the underlying mechanism of RNAi using biochemical and cell biological approaches in both plants and animals, focusing primarily on the processing of dsRNAs into small RNAs and on understanding how related effector complexes can impact gene regulation at so many levels. We also use genetically modified mice to probe the biological functions of the RNAi machinery in mammals. Finally, we combine the information that we and others glean from studies of the interference mechanism to produce highly effective tools that use the RNAi machinery to manipulate gene expression in mammalian cells and animals. These efforts have culminated with the production of nearly genome-wide libraries of RNAi-inducing plasmid vectors covering the mouse and human genomes.