AbstractOligodendrocytes (OLs) are the myelin-forming cells in the central nervous system (CNS) that support neurons through the insulating sheath of axons. This unique feature is achieved by extrinsic and intrinsic gene expression programs during the OL developmental process, in which RNA-binding proteins (RBP) can contribute to dynamic and fine-tuned post-transcriptional regulation. Here, we identified Quaking5 (Qki5) as a master regulator for OL-specific alternative splicing regulation. Qki5 knockdown (KD) led to the exclusion of OL-specific alternative exons and the inclusion of neuron-specific alternative exons. Further analyses indicated that Qki5 contributes to the ratio of pyruvate kinase muscle (PKM) 1/2 through the mutually exclusive exon switching of exon 9 and 10, suggesting that Qki5 regulates lactate metabolism in a cell-type-specific manner. Furthermore, another OL-specific RBP, Secisbp2L (Sbp2L) regulates OL maturation through translational control as another layer of RNA regulation. Sbp2L contributes translational control of the transcription factor Tcf7l2, which plays a role in cholesterol biosynthesis and OL differentiation. These evidence suggest the importance of RNA regulation by cell-type-specific RBP in OL development and function.はじめにオリゴデンドロサイト（OL）は，中枢神経系に存在するグリア細胞の一つであり，主要な機能として神経細胞の軸索に脂質に富んだ髄鞘を形成することで，神経の伝導効率を加速する役割を担っている．加えて，近年では，OL が髄鞘を介して乳酸を供与し，神経細胞にエネルギーを供与していること，さらには神経活動依存的な髄鞘形成が，海馬での記憶の固定化や運動学習に必要であることなど，脳機能との深い関連性が報告され，大変興味深い．OL の発生から分化・成熟に至る分子メカニズムについては，これまでに遺伝学的手法および発生慶應義塾大学殿町先端研究教育連携スクエア・特任講師矢野 佳芳Yoshika YanoKeio University― 233 ―Regulation of Oligodendrocyte-specific lipid metabolismオリゴデンドロサイト特異的脂質代謝制御と多発性硬化症の関連
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