Construction of strategy for rational design of optimized RNA conformational switch

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Konan University
• Principal Investigator: Endoh Tamaki 甲南大学, 先端生命工学研究所, 准教授 (90550236)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RNA / 構造変化 / バイオセンサー / セレクション / 合理設計

Outline of Final Research Achievements

In this research project, rational designing of RNA conformational switches, which enable regulation of functional RNAs in response to a specific molecule, was demonstrated. Light-up aptamers, which bind fluorogens and enhance their fluorescence signals, were utilized as model functional RNAs and converted to the RNA conformational switches to detect the target molecule by the fluorescence signals. Construction of RNA-capturing microsphere particles (R-CAMPs) was first performed to obtain light-up aptamers and optimize the RNA conformational switches. Then, the RNA conformational switches were designed based on the optimized sequence and demonstrated to function in cells to detect the target molecules. The strategy to construct RNA conformational switches demonstrated in this study, can be utilized for regulating RNA functions by external stimulus molecule, contributing a wide range of basic academic RNA research.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

本研究で構築したRNA構造スイッチを活用することで、標的分子の動態を細胞内でリアルタイムに解析するイメージング技術や、特定の外部刺激分子による遺伝子の発現制御技術などを合理的に設計できるようになる。それ故、本研究成果は、分析化学、遺伝子工学、細胞工学など幅広い基礎学術分野への貢献が可能である。加えて、特定の分子に応答した構造変化に基づいて薬理作用を発揮するといった、分子環境応答型の核酸医薬品の開発などにも本研究成果を活用できる。つまり本研究成果は、医工学分野への活用も期待され、その社会的意義は極めて大きい。