Projects

The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

  1. The regulation of SMN function in SMA.

    Principal investigator(s) :
    Dr. Olga Tapia,
    Institution :
    University of Cantabria - Spain
    Grant :
    € 40,000
    Grant Type:
    Fellowship
    Call number :
    8
    Start year :
    2016
    Duration :
    1 year
    Status :
    Ended


    Pic Dr. Tapia - square - smDeletion or mutations of the SMN1 gene cause spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. The survival motor neuron (SMN) protein, encoded by the SMN1 gene, is essential for the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and the molecular assembly of Cajal bodies (CBs). The CB is a nuclear compartment involved in the maturation and assembly of snRNPs implicated in the splicing of protein coding messenger RNAs (mRNA). That is to say that SMN plays an important role in the production of molecules important for the splicing of mRNA, the code for proteins.

    While the role of SMN in the biogenesis of snRNPs has been studied extensively over the past 20 years, very little is known about the regulation of SMN functions by post-translational modifications (PTMs). In particular, the impact of PTMs of SMN on its interactions, protein stability and subcellular localisation. The identity of signaling pathways controlling SMN function in snRNP assembly remains a key question in the field and their elucidation has potential to open novel therapeutic avenues for the treatment of SMA.

    What are the researchers aiming to do?

    Dr. Tapia will seek to understand the regulation of SMN function by PTMs and their implication in the molecular pathophysiology of SMA.

    How will the researchers do this?

    Dr. Tapia will seek to see if the acetylation induced with HDAC inhibitors, nowadays used in SMA therapy, has any impact on SMN PTMs and functional regulation of the protein. In particular, they will determine whether the acetylation state of SMN impacts on its subcellular localization, interactions and stability, as well as on CB biogenesis, assembly of the splicing machinery and transcriptional activity. They will use cultured cells and mouse spinal cord motor neurons, the main target of reduced SMN function in human neuropathology.

    About Dr. Tapia

    Dr. Olga Tapia is a senior post-doctoral scientist at the laboratory of "Cell Biology of the Nucleus" at the University of Cantabria-IDIVAL in Santander (Spain).