Dysfunction of RNA Kinase in Neurodegenerative Diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06871
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Oita University
• Principal Investigator: SHIRAISHI Hiroshi 大分大学, 医学部, 准教授 (80452837)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: RNAキナーゼ

Outline of Final Research Achievements

Cleavage factor polyribonucleotide kinase subunit 1 (CLP1), an RNA kinase, plays essential roles in protein complexes involved in the 3' end formation and polyadenylation of mRNA and the tRNA splicing endonuclease complex, which is involved in precursor tRNA splicing. The mutation R140H in human CLP1 causes pontocerebellar hypoplasia type 10 (PCH10), which is characterized by microcephaly and axonal peripheral neuropathy. We generated knock-in mutant mice that harbored a CLP1 mutation consistent with R140H. We found these mice showed progressive loss of the upper motor neurons, resulting in impaired locomotor activity.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ヒト橋小脳低形成症患者でCLP1変異が発見されていたが、CLP1変異が実際に橋小脳低形成症を発症させるかどうか不明であった。本研究により、CLP1変異が橋小脳低形成症の原因であることが初めて確認された。本研究で作製したCLP1変異マウスがヒト橋小脳低形成症患者の良い動物モデルになり、橋小脳低形成症の発症機序や治療戦略の構築の有用なツールとなると考えられる。また、RNAキナーゼの生理的意義の解明に寄与できると考えられる。