We are investigating the molecular mechanisms of eukaryotic gene expression, with emphasis on transcription and pre-mRNA splicing. Our work focuses both on the nature of biomolecular interactions (protein:DNA, protein:RNA and RNA:RNA) and on the manner in which these interactions cooperate to direct complex processes such as RNA synthesis and processing. We have chosen the genetically and biochemically tractable yeast S. cerevisiae as a model system. Our transcription studies have centered on the influence of chromatin structure on promoter recognition in vivo by RNA polymerase III, which specializes in the synthesis of small RNAs. Recently, we have begun to also study the influence of RNA-binding proteins on transcription elongation by RNA polymerase II. The function of U6 RNA and associated factors in splicing of pre-mRNA is another major interest of my lab. U6 RNA experiences large conformational changes during its interactions with other RNAs in the splicing cycle. We are examining the mechanism and function of these dynamic interactions.
