RNA-protein complexes (RNPs) play key roles in many cellular processes including translation, the regulation of gene expression and chromatin remodelling. Furthermore, an increasing number of diseases have been found to be caused by RNP malfunction, underlining the importance of revealing precise molecular functions of various RNPs.
Our group is interested in understanding the biogenesis, dynamics, nuclear export, function and regulation of several different classes of RNPs in both yeast and mammalian cells. We employ powerful, genome-wide techniques such as UV crosslinking and analysis of cDNA (CRAC) and mass spectrometry to discover new protein-RNA and protein-protein interactions in vivo. Functional analysis is then performed using methods from cell and molecular biology, biochemistry as well as integrative bioinformatics, allowing us to gain insights into the many roles of RNP complexes.
Several projects focus on understanding the biogenesis of ribosomes, in particular by elucidating the functions of key enzymatic factors such as RNA helicases and RNA methyltransferases, which modulate the structure and composition of RNPs or introduce RNA modifications, respectively. Interestingly, recent findings suggest that several of these factors act on multiple classes of RNPs, thereby allowing cross-regulation of different cellular processes. Other projects identify novel functions of human-specific ribosome biogenesis factors and investigate how ribosome production is modulated during development and affected in disease.
A further focus of our work is on revealing the roles that RNA modifications play in the biogenesis, function and dynamics of cellular RNAs and RNPs and in gene expression. Here, we identify RNA targets and study the influence and regulation of proteins that install (“writers”), recognise (“readers”) and remove (“erasers”) modifications in RNAs. Numerous pathogenic mutations in genes encoding RNA modifying enzymes or target RNAs have been identified and we explore the molecular basis of their dysfunction in disease.