Formation and function of nucleolus depending on rRNA G-quadruplexes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21259
• 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: Daisuke Miyoshi 甲南大学, フロンティアサイエンス学部, 教授 (50388758)
• Co-Investigator(Kenkyū-buntansha): 川内 敬子 甲南大学, フロンティアサイエンス学部, 准教授 (40434138)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 核小体 / リボソーム / 核酸 / 四重らせん構造 / 液液相分離 / リガンド

Outline of Final Research Achievements

Nucleolus is essential compartment for responding cellular stresses by controlling biosynthesis of ribosomes. Responsivity and reversibility are critical for nucleolus functions. Interestingly, ribosomal DNA (rDNA) and its transcripts ribosomal RNA (rRNA) posses guanine-rich regions which can fold to form G-quadruplexes (G4s). Noteworthy, RNA and DNA G4s show structural polymorphism, depending on cellular environmental factors. Thus, it is possible to hypothesize that rDNA and rRNA G4s play a critical role to control transcription for ribosome synthesis.
Here we attempted to investigate roles of G4s in formation and function of nucleolus. We found that G4 clusters exist as a core of fibrillar center region, which are the most inner compartment of three layers of nucleolus. Upon cellular stresses, G4s moved to peripherical region to form nucleolar caps. These results demonstrate for the first time that G4 is essential for the formation and function of nucleolus.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

核小体の形成機構や機能には未知な部分が多いが、その解明はがんをはじめとする様々な疾患に対する医薬品開発につながる。本研究では、核小体の形成や機能に、核小体に含まれるDNA（リボソーマルDNA）の形成する構造が重要なことを世界に先駆けて明らかにした。
これらの成果は、新しい抗がん剤の開発につながるだけではなく、核小体という典型的な細胞内液液相分離（水の油が分離するような現象）の機構解明にもつながると期待される。