Elucidation of Ataxin-2-mediated neurodegeneration

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293201
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: Kawahara Yukio 大阪大学, 医学(系)研究科(研究院), 教授 (80542563)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脳神経疾患 / RNA / 脊髄小脳変性症 / 筋萎縮性側索硬化症 / ALS / 神経変性疾患 / 遺伝子 / RNA結合タンパク質

Outline of Final Research Achievements

The gene encoding Ataxin-2 is mutated in the patients with some neurodegenerative diseases, such as spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis. This finding suggests a common pathogenic role of Ataxin-2 in these neurodegenerative diseases. Therefore, a comprehensive understanding of the physiological functions of Ataxin-2 is the first step for elucidating the mechanism underlying Ataxin-2-mediated neurodegeneration. However, although Ataxin-2 has been implicated to be involved in RNA metabolism, the exact biological mechanism and in vivo targets remain unknown. In this study, we identified that Ataxin-2 associates with RNA-induced silencing complex that is required for microRNA-mediated gene silencing. Furthermore, we found that Ataxin-2 binds to distinct elements in the 3’UTRs of target mRNAs. The functional analyses revealed that Ataxin-2 stabilizes target mRNAs, which was attenuated by disease-associated mutations.

Free Research Field

神経科学、RNA生物学