RIBOSOME BIOGENESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ribosome biogenesis is fundamental to cell proliferation and thereby, tumor progression. Cancer cells frequently contain enlarged nucleoli, which are thought to result from increased ribosomal RNA (rRNA). Therefore, decreasing the rate of rRNA synthesis might provide a means of blocking cancer progression. The synthesis of mature rRNA from the pre-rRNA transcript (rRNA processing) is a complex sequential process for which several factors have recently been identified in eukaryotic systems. For many of these factors, the specific role in the rRNA processing has not been determined. The goal of my laboratory is to use X-ray crystallography coupled with biochemical characterization and functional studies to elucidate the molecular functions of rRNA processing factors. To that end, our studies are currently focused on the structure and function of the RIO kinases, which are an ancient group of atypical serine kinases, and Nep1/Emg1, a highly conserved, rRNA-binding, putative methyltransferase. Both groups of proteins are required for the proper maturation of the rRNA of the small ribosomal subunit. We are interested in gathering structural information from crystals of these proteins and their ligands to allow for structure-based functional studies. The structural information obtained from these studies is expected to lead eventually to the structure-based design of inhibitors of ribosome synthesis. Supportted by UMCP start-up funds and NIH