NMR structure determination of a nucleoprotein complex between the human protein muscleblind and myotonic dystrophy associated double stranded RNA

• Antragsteller: Dr. Markus Zeeb
• Fachliche Zuordnung: Biochemie
• Förderung: Förderung von 2006 bis 2007
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 23283272

Myotonic dystrophy (DM) is caused by extensive CUG or CCUG expansions in untranslated regions of certain pre-mRNAs. These expansions form stable double stranded RNA hairpin structures and sequester human muscleblind proteins (MBNL), which regulate alternative splicing of various important pre-mRNAs. The depletion of MBNL from its site of action leads to myotonia, heart blocks, and cataracts that are common features in DM pathogenesis. MBNL contains two pairs of CysCysCysHis zinc finger motifs, which are responsible for RNA binding. The goal of the proposed project is the determination of the three dimensional structure of the MBNL zinc fingers in complex with DM associated double stranded RNA by heteronuclear nuclear magnetic resonance (NMR) spectroscopy. Since MBNL interacts with double stranded RNA and exhibits altered sequence specificity in comparison to homologous single stranded RNA binding zinc finger proteins gaining insights into the structural determinants of these fundamental differences in binding are additional aims of this study.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Peter E. Wright