Profile

Our research is focussed on the molecular mechanisms that govern the transport of eukaryotic RNAs and nuclear proteins from their site of synthesis to their site of function, a process that during interphase allows communication between nuclear transcription and cytosolic translation. We are interested in how specific classes of RNAs are exported from the nucleus at a specific time of their maturation process and how mRNA-binding proteins are imported into the nucleus to take part into the maturation phase of the nucleic acids. The crosstalk of nucleo-cytoplasmic transport with upstream and downstream processes has become increasingly evident. The ‘life’ of an mRNA from its synthesis to its degradation involves a continuous flow of information mediated by subsequent interactions between different macromolecular machineries. In this context, we study the exon junction complex (EJC), a macromolecular assembly that in humans is deposited onto mRNAs upon splicing and is exported together with the nucleic acid to the cytoplasm, where it affects the fate of the mRNA at multiple levels. Components of the EJC are involved in nonsense mediated mRNA decay (NMD), a conserved pathway that detects aberrant mRNAs with premature stop codons (PTCs) and targets them for rapid degradation. We are interested in the mechanisms of NMD (the recognition and targeting of PTC-containing mRNAs) and in the mechanisms of degradation. The exosome is an assembly that degrades RNAs processively in the 3’-5’ direction. We have recently studied the core structure of an archaeal exosome, which shows a barrel-like architecture with sequestered active sites accessible only via an internal channel. The exosome thus appears to function as a nanocompartment for RNA degradation in a similar fashion as the proteasome for protein degradation.