Research

Almost 20% of genetic diseases originate from a post-transcriptionnal misregulation of gene expression that is often correlated with errors in pre-mRNA alternative splicing and/or RNA editing. Alternatively-spliced and edited mRNAs are particularly abundant in the neurons.The finely regulated proportions of the different isoforms of most neurotransmitter receptors, ion channels, neuronal cell surface receptors and adhesion molecules ensure a proper brain function. Several neuron-associated diseases such as FTDP (Frontotemporal Dementia with Parkinsonism) or SMA (Spinal Muscular Atrophy) originate from a single nucleotide mutation in the pre-mRNA resulting in an imbalanced ratio between alternatively-spliced protein variants. The mutations are located in an alternatively-spliced exon and are speculated to weaken critical interactions with a protein splicing factor. The knowledge of parameters involved in these misregulations at the molecular level can help understanding these diseases and finding out new ways of treatment. Our lab is focusing on determining the structures at atomic resolution of such Protein-RNA-complexes using Nuclear Magnetic Resonance spectroscopy (NMR).