Posttranscriptional control of gene expression: pre-rRNA processing, mRNA degradation, splicing and snoRNP assembly in Saccharomyces cerevisiae

Abstract

In eukaryotes, RNAs undergo many processing steps before becoming functional; these steps require specific protein-protein and protein-RNA interactions that are essential for the control of gene expression. We have characterized the function of various yeast proteins, involved in different steps of RNA processing. The RNase named exosome has been the main focus of the research in my group, studying the function of the yeast exosome and the structure of the yeast and archaeal exosome. With this project we propose to continue studying the exosome, mainly the subcellular localization of its subunits and the recruitment of the complex to pre-ribosomal particles. A new challenge is also proposed, that of the study the role of the exosome in mRNA degradation in human cells. We also intend to continue studying Saccharomyces cerevisiae proteins that have been first identified and characterized in our lab, which are involved in various steps of control of gene expression, interconnected by protein interactions. Nop17 is at the center of these interactions, and as a subunit of the co-chaperone complex R2TP, participates in the assembly of multisubunit complexes. Nop17 interacts with the exosome, with splicing factors, snoRNP subunits, pre-60S proteins, and with a protein containing Fe/S clusters. This project is therefore very broad and involves the study of different enzymatic complexes. Given the evolutionary conservation of these processes in eukaryotes, the results obtained here may be later extrapolated to human cells. Importantly, mutations in the genes of orthologs of the proteins studied by us are known to be associated with human genetic diseases. (AU)