Characterization of oligodendroglial sncRNA715 synthesis, its functional role in myelination and identification of novel RNA-transport granule-associated ncRNAs

• Applicant: Professor Dr. Heiko J. Luhmann, since 6/2015
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255307115

Oligodendrocytes myelinate neuronal axons to enable fast and efficient information propagation in the central nervous system. Myelin Basic Protein (MBP) is an essential protein for the process of myelination and its synthesis is tightly controlled to allow localized translation at the plasma membrane in response to neuronal stimuli. We recently identified the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation during oligodendrocyte maturation and intracellular mRNA transport. Importantly, we found that sncRNA715 levels are abnormally high in demyelinated lesions of multiple sclerosis patients which contain MBP mRNA but no protein. We therefore want to understand the synthesis and functional impact of sncRNA715 on myelination in the proposed project. Interestingly sncRNA715 appears to be part of the 47S pre-ribosomal RNA and we plan to characterize its processing in more detail. We further intend to analyze if overexpression and inhibition of sncRNA715 modulate myelin synthesis in myelinating cortical slice cultures. This can be particularly important for the development of novel remyelination therapies in demyelinating diseases. We expect additional mRNAs to be localized in oligodendrocytes which makes it very likely that their translation is inhibited by sncRNAs during intracellular transport and we intend to identify these RNA molecules by RNA sequencing.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1738: Emerging Roles of Non-Coding RNAs in Nervous System Development, Plasticity and Disease
• Participating Person: Professorin Dr. Jacqueline Trotter, Ph.D.
• Ehemaliger Antragsteller: Dr. Robin White, until 5/2015