Grant: CIHR New Investigator

One of the central tenets of biology is that DNA makes RNA, which then makes protein. The DNA sequence in genes is copied into a messenger RNA, whose encoded information is then read by ribosomes, the cellular protein translation machinery, and used to produce proteins. Ribosomes consist themselves of RNA and proteins, and the communication of correct DNA-encoded information, does not only depend on proper conversion of a genes sequence into messenger RNA, but also on the presence of functional ribosomes within cells. Ribosome biogenesis is the process of making ribosomes and involves the coordinated function of over 200 proteins in the synthesis and processing of four ribosomal RNAs, as well as assembly of those ribosomal RNAs with the ribosomal proteins. Incorrect processing and assembly of ribosomal RNAs, which comprise the catalytic part of the protein translation machinery, can result in serious diseases such as various cancers, hematopoietic diseases, and even Altzheimer's Disease. Understanding the molecular mechanisms that define the order of maturation events during ribosome biogenesis is therefore of great interest and importance. The main aim of the proposed research is to study the dynamic changes that take place during the maturation of ribosomal RNA-protein complexes in the unicellular eukaryotic model systems Saccharomyces cerevisiae, which will allow us to gain insight into how the ordered assembly of molecular interactions controls the regulation of ribosome maturation. Since ribosomes and their biogenesis have been highly conserved during evolution, the results from this study will be used in the future to understand how ribosome biogenesis events can affect the development of certain diseases as well as the fate of cells and organisms as a whole.