Grant: Discovery Grants Program - Individual

The long-term goal of my research program is to define the regulation of gene expression in the halophilic archaea at the level of mRNA. As an early branch of the evolutionary tree, the archaea hold a unique evolutionary status. Investigation of RNA metabolic pathways in archaea will therefore provide new insights into the evolution of these pathways, constrain models of the possible transition from RNA-only to RNA-protein molecular machinery, and ultimately allow us to form specific, testable conjectures about biochemical pathways in an RNA world. The immediate objective of this proposal is to investigate archaeal RNA turnover pathways by identification and characterization of ribonucleases and their specific RNA substrates. The identification and characterization of RNases through in vivo and in vitro studies, as well as determination of substrate mRNA secondary structures are key steps in determining the regulation of gene expression in the halophilic archaea at the level of mRNA. Achieving the aims of this proposal will identify proteins involved in the pathways of RNA degradation, as well as identify the interactions and RNA substrates. In addition, any specific secondary structure or specific sequences in the mRNA required for recognition by the degradative enzymes will be identified. This knowledge will further the investigation of gene expression and regulation as controlled through post-transcriptional mechanisms, allow further refinement of RNA structure prediction algorithms, and allow comparison to the known pathways in other systems and further elucidate the evolutionary relationships between the kingdoms of bacteria, eukarya and archaea.