2022 Fiscal Year Final Research Report
Development and utilization of the model system of disease cell for quantitative analysis of nucleic acid structures in cells
| Project/Area Number |
20H02864
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | Konan University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 核酸構造 / 擬似細胞内環境 / 相分離 / 定量的解析 / 神経変性疾患 / 細胞モデル系 |
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| Outline of Final Research Achievements |
Droplets formed in neurodegenerative disease cells contain RNA and peptides with repeat sequences and should exhibit cytotoxicity although the detailed mechanism of droplet formation has not been clarified. In this study, to elucidate the mechanism of droplet formation, we constructed an intracellular molecular environment evaluation system and analyzed the effects of the molecular environment on the structure of nucleic acids and droplet formation. The results indicated that the formation of RNA G-quadruplexeschanged depending on surrounding conditions and showed key roles for droplet formation. Interestingly, the droplet formation was accelerated with increasing the G-quadruplex stability. Our results suggested that changes in the intracellular environment associated with disease progression may alter the structure of nucleic acids and regulate the formation of droplets.
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| Free Research Field |
核酸化学
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| Academic Significance and Societal Importance of the Research Achievements |
核酸の構造は、周辺環境に応答して変化し、遺伝子発現に関わる反応の変異を誘起させる可能性がある。本研究では、核酸の構造が生命現象を制御する機能をもつことを示す一例として、神経変性疾患に関わるRNA構造に焦点をあてた。その結果、細胞毒性に関わる液滴形成を制御する核酸構造を特定することができた。本知見は、細胞毒性を示す凝集体形成を阻害する化合物の合理的な分子設計に有効である。
さらに、本研究で構築した細胞モデル系は、核酸相互作用だけでなく、実細胞内での薬剤と解析対象分子の結合性評価等も簡便に行うことができる。そのため、医療、診断、創薬など実社会に貢献する幅広い応用分野への研究展開が期待される。
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