Developing targeted RNA modification technology

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19234
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Chujo Takeshi 熊本大学, 大学院生命科学研究部(医), 講師 (50788578)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: tRNA修飾 / リボソームRNA / メチル化修飾 / i6A修飾

Outline of Final Research Achievements

We showed that i6A addition to cell culture medium results in i6A incorporation into cellular RNA in 5-FU-resistant human oral squamous cell carcinoma cell line FR2-SAS and its parental 5-FU-sensitive cell line SAS. i6A was predominantly incorporated into rRNAs. Interestingly, at lower i6A concentrations, the cytotoxic effect of i6A was substantially more pronounced in FR2-SAS cells than in SAS cells. Moreover, in FR2-SAS cells, i6A treatment decreased the rate of cellular protein synthesis and increased intracellular protein aggregation, and these effects were more pronounced than in SAS cells. Our work provides insights into the molecular fate of extracellularly applied i6A and suggests investigation of i6A as a candidate for a chemotherapy agent against 5-FU-resistant cancer cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

１番目の結果、つまり標的配列特異的にメチル基を導入できた結果は、遺伝子発現に介入する全く新しい原理の手法を開発できたことを示す。
２番目の結果、つまりi6Aを培地に入れると抗がん剤耐性細胞の一種がその親株よりも死にやすかった結果は、i6Aが抗がん剤耐性がんに対抗するための新たな手段となりうるかもしれない可能性を提示する。