Grant: Project Grant

Loss of a protein named SMN (for 'Survival of Motor Neurons') is responsible for spinal muscular atrophy, a disease that affects 1 in every 10000 newborns and is the leading genetic cause of infant mortality. It is characterized by a degeneration of the motor neurons in the spinal cord, resulting ultimately in muscle weakness, paralysis and death during early childhood. SMN has recently been dubbed 'the master assembler', because it acts as a molecular scaffold to promote the assembly of large macromolecular complexes involved in various cellular processes, related to the biology of RNA. However, this function of SMN should be equally important for all cells and it remains unclear why only spinal cord motor neurons are affected by loss of SMN. It is thought that the many protein-protein interactions in which SMN is involved might be regulated by a protein modification, namely arginine methylation. This has led to the identification of novel functions for SMN and helped us rationalize how deficiencies in functions essential to all cells can cause specific degeneration of the motor neurons of the spinal cord. We are proposing in the current proposal to test the potential of a new strategy for therapeutic intervention, which is based on all the basic science work we have done in the past 10 years.