Genetic regulation by marr transcription factors and YTH proteins that recognize methylated messenger RNA.

摘要

Bacteria use ligand-binding transcriptional regulators to directly integrate environmental stimuli into gene expression programs. The MarR family of regulators, which have diverse ligand-binding activities, are implicated in numerous pathogenic strains as regulators of virulence and antibiotic resistance. The regulatory mechanisms of many MarR proteins remain open to investigation. In Part 1 of this dissertation, we describe the crystal structure of the Salmonella virulence regulator SlyA and discuss implications for SlyA-mediated activation of transcription in the context of infection. We also describe efforts to characterize a MarR regulator of antibiotic resistance in E. coli (Appendix A) and a novel member of the MgrA virulence network in Staphylococcus aureus (Appendix B).;Methylation of mRNA represents a potential new mechanism of genetic control in eukaryotes. In order to clarify this mechanism, it will be important to understand the function of proteins that bind methylated RNA species. In Part 2 of this dissertation, we discuss efforts to purify and crystallize the YTH domain, a highly conserved RNA-binding fold recently identified as a binding partner for methylated RNA.