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

少突胶质细胞为神经轴突提供髓鞘，使信息在中枢神经系统中快速有效地传播。髓鞘碱性蛋白（Myelin Basic Protein， MBP）是髓鞘形成过程中必需的一种蛋白，其合成受到严格控制，以便在神经元刺激下在质膜上进行局部翻译。我们最近发现小非编码RNA715 （sncRNA715）在少突胶质细胞成熟和细胞内mRNA转运过程中是MBP翻译的抑制剂。重要的是，我们发现sncRNA715水平在多发性硬化症患者的脱髓鞘病变中异常高，这些病变含有MBP mRNA但不含蛋白。因此，我们希望在拟建项目中了解sncRNA715对髓鞘形成的合成和功能影响。有趣的是，sncRNA715似乎是47S核糖体前RNA的一部分，我们计划更详细地表征其加工过程。我们进一步打算分析sncRNA715的过表达和抑制是否调节髓鞘皮质切片培养中的髓鞘合成。这对于在脱髓鞘疾病中开发新的髓鞘再生疗法尤其重要。我们预计在少突胶质细胞中会有额外的mrna定位，这使得它们的翻译很可能在细胞内运输过程中被sncRNAs抑制，我们打算通过RNA测序来鉴定这些RNA分子。

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.