Epitranscriptomic regulation of genomic structure R-loop formation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16037
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Okada Shunpei 東京理科大学, 研究推進機構生命医科学研究所, 助教 (40838372)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Rループ / DNA:RNAハイブリッド鎖 / イノシン修飾 / A-to-I RNAエディティング / ADAR1

Outline of Final Research Achievements

Since aberrant accumulation of R-loops in the genome structure can cause adverse effects on cells, the resolution mechanisms of R-loops are very important to cells. It has been suggested that inosine modification, one of the epitranscriptomic marks, is involved in the resolution of the R-loop structure. In this study, we aimed to develop a technique to identify inosine modification sites on the R-loop regions. We found a new compound that specifically reacts with inosine bases, and determined the conditions for biochemical enrichment and purification of nucleic acid oligos cotaining inosine derivatives after the reaction. Furthermore, we explored the R-loop regions resolved by the inosine modification enzyme ADAR1 and found that it resolves the R-loop of the region encoding a transcriptional factor involved in inflammatory responses.

Free Research Field

RNA分子生物学及び生化学

Academic Significance and Societal Importance of the Research Achievements

本研究により既存の手法では困難であったRループ上のイノシン化部位の同定への道が切り拓かれた。イノシン化部位が同定されれば、ヒトゲノムのRループ形成領域の全体像が分かり、Rループ解消の分子機構が明らかになる。Rループの解消の促進は細胞のガン化に関わり、一方、Rループの異常な蓄積は神経変性疾患や自己免疫疾患の発症に繋がる。それゆえ、イノシン修飾を介したRループの解消機構の解明はそれらの疾患の予防・治療法の開発に貢献することが見込まれる。