Construction of novel nucleic acid threaded structures and their application to mRNA protection methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19323
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Tohoku University
• Principal Investigator: Onizuka Kazumitsu 東北大学, 多元物質科学研究所, 准教授 (00707961)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: RNA / 貫通構造体 / ロタキサン / カテナン / フリップアウト / 翻訳

Outline of Final Research Achievements

In this study, we have started research using functional nucleic acids with flip-out ability to construct new nucleic acid-treading structures and explore their functions, with a particular aim to control translation reactions. Although the initially designed molecule showed flip-out ability, it did not result in the formation of a threaded structure. Based on previous findings, we attempted to form a threaded structure into the target RNA by the slipping of a cyclized nucleic acid with tails. We improved the synthesis method and attempted to control translation using newly synthesized cyclized nucleic acids, but no significant change in efficiency was observed. We have succeeded in elucidating the detailed mechanism of formation of the threading structures (pseudorotaxanes and catenanes) and in non-covalent labeling, it is expected that the functionality will be further improved in the future.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

ロタキサンのような貫通構造体の生化学分野への応用に関しては未だ課題が多く、更なるブレイクスルーが必要とされている。環状形態が作り出す貫通構造は分子認識・機能発現にとって理想的な場を構築するため、生体分子に対する機能を備えた貫通構造体形成分子の創製は学術的に価値ある挑戦である。本研究の最終的な成果として、RNAに貫通構造体を形成させることで、共有結合を介さずに効率的に修飾やラベル化が可能になる技術を確立することに成功した。直鎖のRNAだけでなく環状RNAでも同様の修飾を可能にした。これは環状RNAが関与する新たな生命現象の発見・解明やその機能制御に資する生化学ツールとしての応用が期待される。