Mechanism of terminal nucleotidyltransferase

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H03980
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Tomita Kozo 東京大学, 大学院新領域創成科学研究科, 教授 (00345274)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: X線結晶構造解析 / タンパク質 / ＲＮＡ / 複合体 / 分子機構

Outline of Final Research Achievements

In this study, the molecular mechanism of polyU addition to pre-let7 miRNA by TUT4/7, in the presence of Lin28 protein, was clarified by structural and biochemical analysis of the Lin28-interacting region of TUT4/7. The molecular mechanism of polyU addition to the 3' -end of U6 snRNA by TUT1 was also clarified by structural analyses of TUT1 in complex with U6 snRNA, together with the biochemical analysis. We also successfully determined the structure of core region of TENT4/4B, which adds an A/G mix tail to the polyA tail of RNA, providing insight into nucleotide specificity. We also succeeded in determining the structures of various RNA modification enzymes and processing enzymes　and clarified the molecular mechanisms of substrate specificity and regulation of their chemical reactions.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかにしたTUT4/7によるpre-let7のLin28依存的ウリジル化の分子機構はがん抑制作用のあるlet7 miRNAの発現を制御する薬剤開発の基盤になり、また、U6 snRNAの成熟化に関わるTUT1によるウリジル化の分子機構はU6 snRNAの成熟化異常に起因する疾病に対する薬剤の開発の基盤になると期待できる。また、HBCなどのmRNAを安定化させるTENT4A/4Bの特異性の分子機構解明はウイルスの増殖に対する薬剤の開発などの基盤となると期待できる。