Physiological and pathophysiological roles of nonmembrane transport type autophagy

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05146
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Kabuta Tomohiro 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 室長 (70535765)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: オートファジー / RNautophagy / リソソーム / RNA分解

Outline of Final Research Achievements

The mechanism of regulation of putative transporter SIDT2 in RNautophagy was clarified. In addition, We found that the cytoplasmic domain of SIDT2 binds directly to HTT mRNA, the causative gene of Huntington's disease, via the arginine rich motif, and that the binding is polyQ-dependent, and that HTT mRNA is degraded as a substrate of RNautophagy. We performed a detailed analysis of SIDT2 KO mice and searched for SIDT2 mutations in human disease families, and clarified the pathology caused by SIDT2 dysfunction.

Free Research Field

細胞内分解

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで不明であった新規オートファジーの生理・病態生理的意義の解明が進んだ。本研究結果から、RNautophagyは翻訳中あるいは翻訳前のmRNAを分解することができると考えられ、神経変性疾患など疾患の原因となるタンパク質の量を低下させるためにRNautophagyの活性化が応用できる可能性がある。