Molecular basis of 3'-5' polymerase in a diverse RNA recognition

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06519
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: NAKAMURA Akiyoshi 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (10583891)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: X線結晶構造解析 / tRNA修飾 / アミノアシルtRNA合成酵素 / DNA/RNAポリメラーゼ / 核酸 / タンパク質 / 鋳型依存塩基伸長 / 3'-5'方向塩基伸長

Outline of Final Research Achievements

Thg1 is an enzyme that extends nucleotide in the reverse direction. Its biological significance is not fully understood. In our study, we discovered two mechanisms of base recognition in Human Thg1. One mechanism involves the formation of a U:A base pair in tRNA, which has been reported to function as piRNA in breast cancer cells, suggesting a new biological role for reverse polymerization activity. Additionally, the binding between Thg1 and mitochondrial tRNA was found to play a role in base recognition.

Free Research Field

構造生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究ではThg1の逆向きの3’-5’方向へ塩基伸長活性がpiRNA合成と関与することを明らかにし、新たな生体内機能を示唆することができた。さらに、ヒトThg1が様々な修飾塩基をRNAの5’末端に付加できることを明らかにしたことから、ヒトThg1を活用した新たなRNAラベリング技術開発も期待できる。