Do ion channels control the formation of non-canonical nucleic acids and gene expression?

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21258
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Konan University
• Principal Investigator: Sugimoto Naoki 甲南大学, 先端生命工学研究所, 教授 (60206430)
• Co-Investigator(Kenkyū-buntansha): 建石 寿枝 甲南大学, 先端生命工学研究所, 准教授 (20593495)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 核酸非二重らせん / カリウムチャネル / 遺伝子発現機構 / 物理化学的解析 / イオンー核酸相互作用

Outline of Final Research Achievements

The formation of nucleic acids of non-canonical structures induces mutations in biological reactions such as replication, transcription, and translation. In diseased cells, the molecular environments, especially ionic environments, are very different from that of normal cells due to overexpression (or inactivation) of disease-specific ion channels. These environmental differences are thought to affect the formation of non-canonical structures. In this study, we analyzed nucleic acid structures in the environments that mimic the molecular environment in diseased cells using physicochemical methods. As results, we clarified the mechanisms of stability changes of the non-canonical structures by intracellular environmental factors. Furthermore, we developed techniques to control gene expression by ion-nucleic acid interactions using small molecules and modified nucleic acids.

Free Research Field

物理化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、細胞内特有の分子環境が、核酸の構造を変化させ、遺伝子発現に影響を及ぼすことを見出した。さらに、核酸の構造特異的に結合し、がんなどの疾患細胞内環境において、生体反応を制御する核酸や小分子の相互作用を物理化学的観点から明らかにした。これらの知見は、遺伝子発現制御及び薬剤の開発において待望されていた知見であり、核酸構造によって制御される新規の疾患機構制御技術開発に多大な貢献をすると期待される。