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 in 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. We have recently turned our attention to nucleolar structure and morphogenesis.
Ribosome biogenesis is a complex process involving countless reactions, including steps of RNA synthesis, RNA processing, RNA modification, RNP assembly and RNP transport. These reactions require a couple of hundreds of snoRNAs (Small NucleOlar RNAs) and about as much protein trans-acting factors (collectively referred to as RRPs for Ribosomal Rna Processing factors). Over the last few years, we have been deeply involved in the functional characterization of the snoRNAs and the RRPs.
Several Human autoimmune diseases and severe genetic disorders result from mutations in nucleolar antigens involved in ribosome synthesis.