The role of the protein phosphatase PPM1G in the regulation of nuclear functions of the SMN complex
Final Report Abstract
The biogenesis of Uridine-rich small nuclear ribonucleoprotein particles (UsnRNPs) is a complicated process, which requires assembly and maturation steps in the nucleus and in the cytoplasm. Assembly in the cytoplasm is an active process mediated by a macromolecular entity called the SMN complex. The SMN complex is imported together with the snRNPs into the nucleus, where SMN complex proteins accumulate in Cajal bodies (CBs), while snRNPs end up in specialised splicing compartments (“speckles”). Very little is known about the regulation of nuclear functions of the SMN complex. We have identified a nuclear phosphatase, PPM1G, the knockVdown of which results in complete abolishment of the accumulation of the SMN complex in CBs. PPM1G directly interacts with the SMN complex and is responsible compartment specific dephosphorylation of SMN complex proteins. Identification of PPM1G enables us to specifically search for kinase activities, which phosphorylate components of the SMN complex and which are required for SMN accumulation in CBs. We are also aiming to identify amino acid residues in SMN complex proteins, which are responsible for this regulation. In the second part of our project, we are going to test whether PPM1G knockVdown changes the dynamics of SMN within the nucleus and, possibly, regulates its capability to return to the cytoplasm. Furthermore, we will test SMN and PPM1Gs role to help maturation of UsnRNPs. Finally, we are going to investigate the function of PPM1G and other phosphatases in the regulation of the nuclear splicing machinery.
