Investigating protein complexes potentially governing microtubule-dependent mbp mrna distribution

• Autores: Bogumila Jagiello
• Directores de la Tesis: Sebastian Maurer-Stroh (dir. tes.)
• Lectura: En la Universitat Pompeu Fabra ( España ) en 2018
• Idioma: español
• Tribunal Calificador de la Tesis: Jens Lüders (presid.), Verena Ruprecht (secret.), Carme Gallego Gonzalez (voc.)
• Materias:
  • Química
    • Bioquímica
      • Proteínas
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • Localization of mRNA molecules enables locally and temporally regulated protein synthesis, which is vital for many fundamental cellular processes. In oligodendrocytes transport of myelin basic protein (MBP) mRNA to myelinating processes allows for local synthesis of MBP. MBP has an essential function if forming the myelin sheath that surrounds axons, nurtures the nerve cells and allows for fast stimuli transmission. Despite extensive research about the molecular mechanisms that guide the transport and local expression of MBP-mRNA it is still not clear how this mRNA is transported to its destination and how activation of translation at the right place is controlled. Using the information from published data and an interaction screen performed in the lab we selected two protein complexes essential for MBP mRNA localisation and attempted to build them from bottom-up. In this approach in vitro reconstitution of the minimal complexes allows us to analyse the function of each component of the complex and understanding better how biological processes are regulated.

    MBP mRNA synthesis is partially dependent on the interaction between an RNA binding protein, hnRNPA2, and a microtubule polymerase, chTOG. To elucidate the mechanism by which this interaction triggers MBP mRNA translation we decided to analyse the functional consequences of this entirely novel interaction between a microtubule binding and RNA binding protein. I successfully produced functional recombinant hnRNPA2 and chTOG. The interaction detected between those two proteins turned out to be unspecific.

    I hypothesize it is due to the conformation that hnRNPA2 acquires in the RNP granule or depends on other components. Due to the lack of resources to investigate this further we suspended this project.

    Delivery of MBP mRNA to the oligodendrocytes processes is maintained by microtubuledependent kinesin motors. The kinesin Kif1Bβ has been shown to carry out the transport.