Effect of large ribosomal subunit proteins on ribosome biogenesis and cell cycle

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Ribosome biogenesis and cell cycle are coordinated processes. Recent studies in mammalian cell lines have showed that ribosome biogenesis is linked to tumorgenesis, where mutation or depletion of ribosomal factors, leads cancer cell proliferation. The yeast Saccharomyces cerevisae is a useful model organism for understanding the connections between ribosome biogenesis and cell cycle control. Only a handful of studies have been done and these have mainly focused on different transacting factors involved in ribosome biogenesis. Here we are focusing on the role of ribosomal proteins. Our lab has found that depleting the ribosomal protein Rpl4 results in defects in both rRNA processing and cell cycle with accumulation of di‐ and tri‐ budded cells. This discovery has led our lab to investigate other ribosomal proteins also have implications in these two cellular pathways. Depletion of ribosomal proteins Rpl7A, Rpl18A, Rpl37, Rpl40A in S. cerevisae also resulted in yeast cells with di‐ and tri‐ buds, unlike the wild type cells, which only produce a single bud at a time. To fully understand which stage of cell cycle is defective, fluorescent activated cell sorter and microscopy analysis are in progress. We are currently characterizing defects in rRNA processing and ribosomal subunit assembly during depletion of these ribosomal proteins.