Biochemical and Genetic Characterization of Ribosome Biogenesis and Functional Diversity

Ribosome heterogeneity, characterized by variations in ribosomal protein composition, rRNA sequence, and rRNA modifications, plays a crucial role in shaping translational control and cellular function. These subtle differences can alter how ribosomes prioritize mRNA translation and respond to various environmental stimuli. In our research, we use an integrated approach to study different aspects of ribosome heterogeneity by employing both yeast and human cells. In yeast (Saccharomyces cerevisiae), we focus on understanding how the expression of duplicated ribosomal protein genes and their differential regulation contribute to ribosome diversity, particularly under stress conditions. In human cells, we investigate how snoRNA-guided rRNA modifications affect ribosome function and cancer progression. Our findings have shown that minor paralogs of ribosomal proteins, which are non-essential under normal conditions, become critical during stress, suggesting a specialized role in modulating the translational machinery. By examining rRNA modifications in human cells and protein composition in yeast, we aim to elucidate how these variations impact ribosome biogenesis, translation, and overall cellular function. This research offers insights into the role of ribosome heterogeneity in both fundamental biology and disease states, including cancer, where dysregulation of ribosome function can drive tumorigenesis and offer potential targets for therapeutic intervention.