The role of non-coding RNAs in skeletal development and disease

• Antragsteller: Professor Dr. Bernhard Zabel
• Mitantragsteller: Dr. Tim J. M. Welting
• Fachliche Zuordnung: Kinder- und Jugendmedizin
• Förderung: Förderung von 2012 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 211806425

The ribonuclease mitochondrial RNA-processing (RMRP) gene encodes the RNA component of a multiprotein-RNA complex termed RNase MRP. The RNase MRP complex is implicated in various cellular processes, as diverse as ribosomal biogenesis, mitochondrial RNA cleavage, cell cycle regulation, and possibly telomerase function. Mutations in the RMRP gene are the cause of the condition Cartilage Hair Hypoplasia, the first human disease known to be caused by mutations in a non-coding RNA molecule (CHH, MIM #250250). CHH is a rare autosomal recessive condition characterized by short stature and highly variable extraskeletal features, including immunodeficiency and a predisposition to malignancy. Although short stature is the leading CHH symptom, the functional role of RMRP in skeletal development remains unknown. Within the proposed research programme, we aim to unravel the mechanisms by which RMRP gene mutations cause CHH. Main specific objectives of our work plan are to determine the physiological RNase MRP function in endochondral ossification and the molecular consequences of disease-associated RMRP mutations in chondrogenic cellular systems, patient-derived primary cells and conditional mouse lines. Based on results obtained from these CHH disease models, our long-term goal is to identify novel therapeutic options. As the role of non-coding RNAs in skeletogenesis and bone disorders is a largely unexplored scientific area, our project will contribute to the development of a novel research field.

• DFG-Verfahren: Sachbeihilfen
• Internationaler Bezug: Niederlande