Ribosomal RNA processing and modification
Groupleader: Martin Ko
RIBOSOME BIOGENESIS IN CELL GROWTH, DISEASE AND AGEING
Ribosome biogenesis is an essential major metabolic process in all organisms. The making of ribosomes in eukaryotes requires the coordinated action of all three RNA polymerases, numerous small nucleolar RNAs (snoRNAs) and several hundred protein factors. The highly dynamic and complex pathway of ribosome synthesis is directly or indirectly linked to various celullar processes.
The goal of the lab is to extend our understanding of molecular mechanism underlying the ribosome biogenesis and its regulation in healthy and pathological situations. We are interested in the following aspects of ribosome biogenesis:
Regulation of ribosome synthesis; nucleolar stress and usage of alternative pathways in development and disease.
Role of RNA modifications and snoRNAs.
Specialized ribosomes – formation and function? Role in ageing?
In the recent years it has become clear that ribosomes with differently modified rRNA or diverse protein composition coexist in cells. It has been proposed that these distinct ribosomes might be specialized for translation of a subset of mRNAs. We want to answer the following critical questions: Is the formation of different ribosomes regulated or is it a consequence (“side effect”) of the complex process of ribosome assembly with many steps occurring presumably stochastically? Do these different ribosomes have specific functions? With our colleagues we have recently reported that expression of the cytosine specific methyltransferase Rcm1/NSUN5 is reduced in stressed cells and during senescence. Importantly, deletion of Rcm1/NSUN5 increases the life-span and oxidative stress resistance. We therefore use aged and induced senescent cells as one of the model systems to investigate the role of differently modified ribosomes.