Detailseite
Projekt
Molecular dissection of the assembly pathway of spliceosomal U snRNPs
Antragsteller
Professor Dr. Utz Fischer
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2004 bis 2007
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5468076
The assembly of spliceosomal snRNPs, albeit spontaneous in vitro, has recently been shown to depend on the aid of a macromolecular protein complex in vivo. This complex, named after SMN, the protein affected in the neuromuscular disease spinal muscular atrophy, facilitates the cytoplasmic assembly of snRNPs in an ATP-dependent reaction. In this process, spliceosomal Sm proteins, which constitute the protein core of U snRNPs, must bind to the SMN-complex prior to their transfer onto the U snRNA. A second com plex, termed after its methyltransferase PRMT5, functionally regulates the SMN-complex. The PRMT5-complex catalyses the symmetric dimethlyation of arginines in Sm proteins B/B', D1 and D3, thereby increasing their affinity for the SMN-complex. This project is designed to provide a better understanding of the mechanism of the assembly reaction, and to elucidate functions of individual complex components during this process. A prerequisite for these studies has recently been accomplished through the developme nt of an in-vitro-system that recapitulates U snRNP-assembly and through the generation of mutant SMN-complexes. In addition, RNA-interference studies will be conducted to test the hypothesis that the SMN/PRMT5-system may not only act as an assembly factor, but also as a chaperone preventing aggregation of Sm proteins and/or misassembly to non-snRNA targets. Finally, we will address whether the formation of other RNPs requires assisting factors akin to the SMN/PRMT5 system.
DFG-Verfahren
Forschungsgruppen
