Grant: Discovery Grants Program - Individual

Ribosomes are the organelles that synthesize proteins in all living organisms. They are formed by the association of two subunits, and each is constituted of large RNA molecules and multiple proteins. The key components of ribosomes are the ribosomal RNAs (rRNAs), which are directly involved in the different steps of protein synthesis. In fact, most antibiotics target rRNAs to perturb protein synthesis. The biogenesis of ribosomes is a major cellular process, and it is a prerequisite for cells to grow in size and proliferate. In eukaryotes, this process takes place in the nucleolus, a prominent compartment of the cell nucleus. The majority of nucleolar factors function at various steps of the intricate pathway that leads to the production of ribosomes. But the nucleolus is not merely a ribosome factory: many other cellular processes are connected to the nucleolus, such as viral replication, aging and cell cycle control. My research program focuses on ribosome biogenesis and nucleolar function. For these studies we use the baker's yeast Saccharomyces cerevisiae because it is the best studied model system in the field. Indeed, yeast is a simple eukaryote and we can take advantage of its well-characterized genetics, in combination with powerful biochemical and molecular biology tools. One of the major tasks of my laboratory is to understand the early events of ribosome formation, and to decipher the molecular mechanisms involving nucleolar factors that participate in the production of mature rRNAs. For the next five years we will work on highly conserved nucleolar factors: the RNA helicase Dbp4, the RNA acetyltransferase Kre33, and ribosomal protein S18, all of which are necessary to form the small ribosomal subunit. We have also initiated studies on two nucleolar RNA methyltransferases that we call Nop38 and Nop36; these enzymes are highly conserved, yet their target(s) are not known, but we have indications they could have a role in ribosome biogenesis. Our research on these nucleolar factors is important to understand how they function in the cell: elucidation of molecular mechanisms underlying ribosome biogenesis in eukaryotes could open new avenues to improve the growth of cells or target eukaryotic pathogens that affect plants and other animals.