Analysis of the molecular mechanisms of RNA-directed DNA methylation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06159
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Molecular biology
• Research Institution: The University of Tokyo
• Principal Investigator: Iwakawa Hiro-oki 東京大学, 定量生命科学研究所, 助教 (60710415)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: RNAサイレンシング / siRNA / DNA-RNAハイブリッド

Outline of Final Research Achievements

We conducted our research by focusing on how RNA-induced silencing complexes (RISCs) mediate sequence specific DNA methylation in nuclei. Through in vitro binding assays, we found that the plant cytoplasmic RISCs interact more tightly with RNAs than with DNAs, conversely, the plant nuclear RISCs bind to DNAs with much higher affinity than to RNAs. Moreover, we obtained novel insights into nuclear RISC assembly and template specificity of RNA-dependent RNA polymerase 6 (RDR6), which is known to be involved in de novo DNA methylation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

植物の核内RISCがRNAよりもDNAと強く結合することを世界で初めて生化学的に示したことで、「核内RISCは新生RNAとの結合を介して標的DNAに接近しメチル化を促進する」と信じられてきた従来のモデルを書き換える可能性がある。さらに核内RISC形成機構やRDR6の鋳型特異性の生化学的な理解は、未だ多くの謎に包まれている核内RNAサイレンシング機構を理解する上で重要な基盤的知見となる。