Verification of the 'RNA metabolic relay disorder' hypothesis in Frontotemporal Dementia.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03602
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Osaka University
• Principal Investigator: Mori Kohji 大阪大学, 大学院医学系研究科, 講師 (40775318)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 前頭側頭葉変性症 / RNA代謝 / 近接ビオチン化法 / C9orf72

Outline of Final Research Achievements

The C9orf72 repeat expansion mutation is a major causative genetic mutation in familial frontotemporal lobar degeneration (frontotemporal dementia) and amyotrophic lateral sclerosis. We have previously found that the pathogenic GGGGCC repeat RNA-binding protein hnRNPA3 promotes repeat RNA metabolism, but the mechanism is unknown. In this study, we used a combination of proximal biotinylation and mass spectrometry to comprehensively delineate the neighbourhood of hnRNPA3 and identify a promising novel factor involved in GGGGCC repeat RNA metabolism.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

C9orf72変異型の前頭側頭葉変性症・筋萎縮性側索硬化症では、細胞内に病原性GGGGCCリピートRNAが蓄積されている。GGGGCCリピートRNAの分解を促進することができれば、新たな治療法の開発につながる。本研究はいまだ不明な点が多い、GGGGCCリピートRNAの代謝経路の一端を明らかにしたものである。本研究の成果を応用し、RNA分解の観点からC9orf72変異型の前頭側頭葉変性症・筋萎縮性側索硬化症の新たな治療法の開発につなげていきたい。