Development of basic technology for intractable and rare diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22601
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: University of the Ryukyus (2021); Yokohama City University (2019-2020)
• Principal Investigator: YAMASHITA AKIO 琉球大学, 医学(系)研究科(研究院), 教授 (20405020)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: mRNA分解 / mRNA翻訳 / ナンセンス変異 / mRNA監視機構 / 嚢胞性線維症

Outline of Final Research Achievements

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that eliminates aberrant mRNAs containing premature termination codons (PTCs). NMD inhibits the production of aberrant proteins that still retain, at least in part, wild-type function as well as dominant-negative peptides. Therefore, the selective inhibition of NMD has the potential to ameliorate NMD-exacerbated mutant phenotypes. However, we do not have sufficient knowledge of how to effectively suppress NMD with minimum cytotoxic effects. In present study, we identified several approved drugs which can repress NMD activity in cells. These drugs are previously not linked with NMD.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた、複数のmRNA監視機構を阻害する臨床薬は、これまで、NMDとの関わりがわかっていなかった化合物であり、培養細胞レベルではあるが、新たなNMD阻害法の発見となった。このmRNA監視機構阻害法は、臨床で用いられる薬剤による物であるため、安全性などの情報が得られている。今後、動物モデルを用いたmRNA監視機構抑制の検証後、早期に人における応用へつなげられる事が期待される。