We study RNA catalysts and RNA-mediated cellular processes. With regard to the ability of RNA to catalyze reactions, we want to know the types of reactions that RNA can catalyze and how easy it is for new RNA enzymes (ribozymes) to emerge. Knowledge of the intrinsic catalytic abilities of RNA provides a backdrop for understanding biocatalysis and is critical for evaluating current notions of life's origins and early evolution. Our studies often include in vitro selection experiments, which allow us to isolate very rare catalytic molecules from very large libraries of different sequences. For example, we have generated a ribozyme that synthesizes small pieces of RNA, supporting the idea of RNA self-replication in the early evolution of life.
With regard to RNA-mediated cellular processes, we are currently studying endogenous gene silencing mediated by RNA, including targeted mRNA degradation (RNAi), and a class of tiny noncoding RNAs with regulatory roles in eukaryotes (microRNAs). Most recently we have identified hundreds of microRNA genes in animals and plants. We are currently combining biochemical, molecular, genetic, and computational approaches to identify additional genes, explore their roles in regulating eukaryotic gene expression, and determine the molecular mechanisms of their action.
