The effect of non-canonical structure of nucleic acids on liquid-liquid phase separation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23639
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0501:Physical chemistry, functional solid state chemistry, organic chemistry, polymers, organic materials, biomolecular chemistry, and related fields
• Research Institution: Konan University
• Principal Investigator: Matsumoto Saki 甲南大学, 先端生命工学研究所, 特任教員(助教) (50850822)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: DNA / RNA / 核酸高次構造 / 遺伝子発現制御

Outline of Final Research Achievements

The membrane-less organelles (droplets) in cells has been suggested to be involved in various biological phenomena, such as the regulation of gene expression, and also to contribute to the pathogenesis of cancer and neurodegenerative diseases. Most droplets contain nucleic acids, but there is still no general rule that explains the properties of these nucleic acids and the effect of nucleic acids on the properties of droplets. In this study, we aimed to elucidate the mechanism of droplet formation and disappearance from the viewpoint of structural changes of nucleic acids.
We focused on G-quadruplexes, which is one of the non-canonical structures of nucleic acids, and systematically investigated its properties. The results suggest that the number of guanine quartets in the structure has different effects on droplet formation.

Free Research Field

核酸化学、生体関連化学

Academic Significance and Societal Importance of the Research Achievements

細胞内に存在する液滴は、認知症やアルツハイマー病などの神経変性疾患を引き起こすアミロイド形成に関わる。RNAグアニン四重らせん（G4）は、液滴形成に関わるRNA配列中に存在する核酸の高次構造の一つであり、本研究ではRNA G4に着目して、この構造の周辺環境への応答、液滴形成への影響を調べた。その結果、G4に含まれるグアニンカルテットの枚数により、周辺環境の変化への応答が異なることが明らかになった。この結果は、RNA G4が液滴形成に与える影響が、グアニンカルテットの枚数で異なることを示唆するものであり、RNA G4の疾患への影響解明やRNA G4を標的とした創薬研究の基盤となる成果である。