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 sncRNA715 合成的表征、其在髓鞘形成中的功能作用以及新型 RNA 转运颗粒相关 ncRNA 的鉴定

• 批准号: 255307115
• 负责人: Professor Dr. Heiko J. Luhmann, since 6/2015
• 金额: --
• 依托单位: Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/255307115?language=en
• 关键词: Characterization; oligodendroglial; sncRNA715; synthesis; its

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.

少突胶质细胞使神经元轴突髓鞘，使信息在中枢神经系统中快速有效地传播。髓鞘碱性蛋白(MBP)是髓鞘形成过程中必不可少的一种蛋白质，其合成受到严格控制，以允许在质膜上局部翻译，以响应神经元的刺激。我们最近发现小的非编码RNA 715(SncRNA715)是在少突胶质细胞成熟和细胞内mRNA运输过程中MBP翻译的抑制因子。重要的是，我们发现多发性硬化症患者脱髓鞘病变中SncRNA715水平异常高，这些病变含有MBP mRNA而不含蛋白。因此，我们想要了解SncRNA715在拟议的项目中对髓鞘形成的合成和功能影响。有趣的是，SncRNA715似乎是47S前核糖体RNA的一部分，我们计划更详细地描述它的加工过程。我们进一步打算分析是否过表达和抑制SNcRNA715在髓鞘皮质切片培养中调节髓鞘的合成。这对于开发新的脱髓鞘疾病的再髓鞘疗法特别重要。我们预计更多的mRNAs定位于少突胶质细胞中，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测序来识别这些RNA分子。