Research Project
7071954
[unreadable] DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the role of non-ribosomal proteins in the assembly and nuclear export of eukaryotic ribosomal subunits. Ribosomes are among the largest and most complex ribonuclear-protein machines assembled in eukaryotes. The basic outline of ribosome biogenesis seems conserved throughout eukaryotes, but most of our current understanding of this process comes from studies in yeast. Ribosome assembly in yeast takes place in the nucleolus and involves a series of highly coordinated rRNA processing and modification events that are coupled to the assembly of some 80 ribosomal proteins. Assembly and export requires the participation of over 150 non-ribosomal proteins. Our previous work demonstrated that yeast strains lacking non-ribosomal proteins Yar1 or Ltv1 are hyper-sensitive to stress and defective in 40S ribosome biogenesis. We have recently assembled considerable evidence implicating Ltv1 in the nuclear export of pre-403 ribosomal subunits. The key questions we address in this proposal are the following: 1) Is 40S subunit export inhibited in delta Itv1 mutants? 2) Is Ltv1 a direct target for the Crm1 exporter in vivo? Does Ltv1 have an NES sequence to which Crm1 binds? 3) What is the function of the interaction between Ltv1 and ribosomal protein, RpS3? Does RpS3 serve as a dock on the small subunit for Ltv1 -mediated export? 4) Are there multiple pathways for 40S export? The results of this project may be expected to have significance beyond understanding ribosome synthesis in yeast. Ribosome biogenesis is closely coupled in all cells to growth rate and cell division. The synthesis of ribosomes represents a major fraction of the total biosynthetic output in rapidly dividing cells, and is down-regulated immediately in response to limiting nutrients or environmental stress. Conversely, the rate of cell division is ultimately limited by the rate of ribosome biogenesis, as a high concentration of ribosomes is necessary to meet the protein biosynthesis demands of rapidly dividing cells. Understanding the mechanisms underlying ribosome biogenesis may thus provide new targets for limiting the growth of such rapidly dividing cells as cancerous tumor cells. [unreadable] [unreadable] [unreadable]
