RNAs (RiboNucleic Acids) are central to gene expression. In the cells, RNAs all work in close association with proteins within so-called RNPs (RiboNucleoProtein particles). It doesn’t matter how big or small an RNA is, or at which steps of gene expression it is involved; RNAs are always intimately connected to proteins.
In the Lab, we are trying to understand how RNPs are put together and function.
Most of our work so far has focused on a very large RNP called the Ribosome. The Ribosome is made of two subunits of unequal size, each carrying specialized functions in translation. Translation is a key step of gene expression that converts the genetic information encoded in nucleic acids into proteins.
We are focusing our attention on Ribosome Synthesis in Eukaryotes. Eukaryotic cells are compartmentalized in several functional domains that are more or less separated physically. Although ribosome synthesis involves most cellular compartments, many of the initial steps occur in a specialized nuclear domain, the Nucleolus. The nucleolus is a highly dynamic organelle that that is reassembled at the end of each mitosis in mammals. We have recently turned our attention to nucleolar structure and morphogenesis.
Numerous human diseases have been linked to defects in ribosome synthesis. These are the so-called ‘Ribosomopathies’, including several aplasias (red blood cell maturation defects), bone-marrow failure, and other disorders. The major site of ribosome synthesis, the nucleolus, has known functions in cell-cycle regulation and tumour surveillance pathways, and several nucleolar antigens have been notoriously linked to blood cancers. Here the aim is to understand how human ribosomes assemble and function in Health & Disease. We want to find out what the nucleolus has to “tell” tumour pathologists and to define communalities and specificities between human ribogenesis and that of budding yeast.