Feedback regulation between RNA biogenesis and lipid metabolism in oligodendrocyte differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Niigata University
• Principal Investigator: Hayakawa-Yano Yoshika (早川佳芳) 新潟大学, 医歯学系, 特任助教 (60397320)
• Co-Investigator(Kenkyū-buntansha): 矢野 真人 新潟大学, 医歯学系, 准教授 (20445414)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 希突起膠細胞 / 髄鞘形成 / RNA制御 / 脂質代謝

Outline of Final Research Achievements

To identify novel RNA binding proteins (RBPs) with oligodendrocytes (OLs)-specific and OLs differentiation stage-dependent expression, we performed pSI screening based on transcriptome information of OLs and other-type of neural cells. We successfully identified a new RBP, named Rochs, which is specifically expressed in OLs with the differentiation dependency.
In this study, we performed loss-of-function studies in cultured mouse OPC and mouse genetics and found that Rochs regulates lipid metabolism and OLs differentiation. Furthermore, our study identified that Rochs promotes OLs differentiation through the interaction with mRNA of a major regulator, which encodes a transcription factor related to lipid metabolism and OLs maturation. We believe that our present findings provide a novel molecular mechanism to understand OLs maturation, as well as diseases including myelination deficiency and demyelinating disorders.

Free Research Field

分子神経生物学

Academic Significance and Societal Importance of the Research Achievements

脱髄性疾患の一つである多発性硬化症は希突起膠細胞(OLs)が形成する髄鞘が障害され、脱髄と寛解を繰り返し進行する難治性疾患であり、未だ病態の解明には至っていない。我々は、OLsの分化段階および神経系での様々な細胞種ごとのトランスクリプトーム情報からpSI解析を行い、OLsの分化に伴って発現が変動する新規RNA結合蛋白質としてRochsを同定した。さらに本研究により、Rochsは重要な制御因子のmRNAへの結合を介してOLsの成熟を正に制御する分子であることが明らかになり、髄鞘形成不全症や脱髄性疾患の分子基盤の解明に繋がる基礎的な知見が得られた。