Structure and Function of RNase MRP

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0077949LindahlRibosomes, the protein-synthesizing machines of all cells, are essential for cellular growth and survival. The biogenesis of ribosomes has been related to growth rate, development, and even disease and aging. Therefore, it is important to understand the process of ribosome formation. The synthesis of these complex organelles requires a series of activities, including processing of the precursor rRNA transcript, modification of specific nucleotides, and assembly of rRNA with 50-80 proteins. The key features of ribosome biogenesis are shared in all eukaryotes from yeast to humans, allowing one to make generalizations from what has been learned in studies of model organisms. In this project, Saccharomyces cerevisiae has been chosen as the experimental organism because of its well-developed systems for genetic manipulation. These studies will focus on the structure and function of RNase MRP, an enzyme that cleaves the precursor rRNA in the Internal Transcribed Spacer between the sequences destined for small and large ribosomal subunits. This nucleolar enzyme contains one RNA subunit and nine proteins. The architecture and mechanism of action of RNase MRP are poorly understood. The PI will use phylogenetic sequence comparisons, mutant analysis, immunoprecipitation and protein tagging to analyze how each protein subunit and territories of the RNA subunit contribute to enzyme structure and substrate specificity. The genetic approach will be complemented with RNA structure probing and computer analysis of RNA structure and protein-RNA interactions. The final goal is to provide a model for the structure and function of RNase MRP.