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Mechanism of terminal nucleotidyltransferase

Research Project

Project/Area Number 18H03980
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionThe 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
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥43,810,000 (Direct Cost: ¥33,700,000、Indirect Cost: ¥10,110,000)
Fiscal Year 2021: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2020: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2019: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2018: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsX線結晶構造解析 / タンパク質 / RNA / 複合体 / 分子機構 / RNA / X線結晶解析 / 修飾酵素 / プロセシング / 結晶構造解析 / 蛋白質 / 構造 / 機能 / X線 / 構造解析 / 機能解析 / RNA-蛋白質複合体 / X線構造解析 / ノンコーディング / 鋳型非依存 / 機能制御
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.

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。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mechanistic insights into tRNA cleavage by a contact-dependent growth inhibitor protein and translation factors2022

    • Author(s)
      Wang Jing、Yashiro Yuka、Sakaguchi Yuriko、Suzuki Tsutomu、Tomita Kozo
    • Journal Title

      Nucleic Acids Research

      Volume: - Issue: 8 Pages: 4713-4731

    • DOI

      10.1093/nar/gkac228

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reversible RNA phosphorylation stabilizes tRNA for cellular thermotolerance2022

    • Author(s)
      Takayuki Ohira, Keiichi Minowa, Kei Sugiyama, Seisuke Yamashita, Yuriko Sakaguchi, Kenjyo Miyauchi, Ryo Noguchi, Akira Kaneko, Izumi Orita, Toshiaki Fukui, Kozo Tomita,Tsutomu Suzuki
    • Journal Title

      Nature

      Volume: - Issue: 7909 Pages: 372-379

    • DOI

      10.1038/s41586-022-04677-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular basis of glycyl-tRNAGly acetylation by TacT from Salmonella Typhimurium2021

    • Author(s)
      Yashiro Y, Zhang C, Sakaguchi Y, Suzuki T, Tomita K.
    • Journal Title

      Cell Rep.

      Volume: 37(12) Issue: 12 Pages: 110130-110130

    • DOI

      10.1016/j.celrep.2021.110130

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanism of aminoacyl-tRNA acetylation by an aminoacyl-tRNA acetyltransferase AtaT from enterohemorrhagic E. coli.2020

    • Author(s)
      Yashiro Y, Sakaguchi Y, Suzuki T, Tomita K.
    • Journal Title

      Nat Commun.

      Volume: 11 Issue: 1 Pages: 5438-5438

    • DOI

      10.1038/s41467-020-19281-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The tRNA pseudouridine synthase TruB1 regulates the maturation of let‐7 miRNA2020

    • Author(s)
      Kurimoto Ryota、Chiba Tomoki、Ito Yoshiaki、Matsushima Takahide、Yano Yuki、Miyata Kohei、Yashiro Yuka、Suzuki Tsutomu、Tomita Kozo、Asahara Hiroshi
    • Journal Title

      The EMBO Journal

      Volume: 39 Issue: 20

    • DOI

      10.15252/embj.2020104708

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Substrate specificities of Escherichia coli ItaT that acetylates aminoacyl-tRNAs.2020

    • Author(s)
      Zhang C, Yashiro Y, Sakaguchi Y, Suzuki T, Tomita K.
    • Journal Title

      Nucleic Acids Res.

      Volume: 48 Pages: 7532-7544

    • DOI

      10.1093/nar/gkaa487

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanistic insights into m6A modification of U6 snRNA by human METTL162020

    • Author(s)
      Aoyama Tomohiko、Yamashita Seisuke、Tomita Kozo
    • Journal Title

      Nucleic Acids Research

      Volume: - Issue: 9 Pages: 5157-5168

    • DOI

      10.1093/nar/gkaa227

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro yeast reconstituted translation system reveals function of eIF5A for synthesis of long polypeptide2020

    • Author(s)
      Abe Taisho、Nagai Riku、Shimazaki Shunta、Kondo Shunta、Nishimura Satoshi、Sakaguchi Yuriko、Suzuki Tsutomu、Imataka Hiroaki、Tomita Kozo、Takeuchi-Tomita Nono
    • Journal Title

      The Journal of Biochemistry

      Volume: 167 Issue: 5 Pages: 451-462

    • DOI

      10.1093/jb/mvaa022

    • NAID

      40022226787

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of human cytoplasmic tRNAHis-specific 5′-monomethylphosphate capping enzyme2020

    • Author(s)
      Liu Yining、Martinez Anna、Yamashita Seisuke、Tomita Kozo
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 3 Pages: 1572-1582

    • DOI

      10.1093/nar/gkz1216

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulatory mechanism of the toxin targeting aminoacyl tRNA2019

    • Author(s)
      八代 悠歌、富田 耕造
    • Journal Title

      生化学

      Volume: 91 Issue: 6 Pages: 810-814

    • DOI

      10.14952/SEIKAGAKU.2019.910810

    • NAID

      40022117305

    • ISSN
      0037-1017
    • Year and Date
      2019-12-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of the Lin28-interacting module of human terminal uridylyltransferase that regulates let-7 expression2019

    • Author(s)
      Yamashita Seisuke、Nagaike Takashi、Tomita Kozo
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1960-1960

    • DOI

      10.1038/s41467-019-09966-5

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of the enterohemorrhagic Escherichia coli AtaT-AtaR toxin-antitoxin complex.2019

    • Author(s)
      Yashiro Y, Yamashita S, Tomita K.
    • Journal Title

      Structure

      Volume: 27 Issue: 3 Pages: 476-484

    • DOI

      10.1016/j.str.2018.11.005

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Function and Regulation of Human Terminal Uridylyltransferases.2018

    • Author(s)
      Yashiro Y, Tomita K.
    • Journal Title

      Front. Genet.

      Volume: - Pages: 538-551

    • DOI

      10.3389/fgene.2018.00538

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acetate-dependent tRNA acetylation required for decoding fidelity in protein synthesis2018

    • Author(s)
      Taniguchi T, Miyauchi K, Sakaguchi Y, Yamashita S, Soma A, Tomita K, Suzuki T
    • Journal Title

      Nature Chemical Biology

      Volume: 14 Issue: 11 Pages: 1010-1020

    • DOI

      10.1038/s41589-018-0119-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human BCDIN3D is a cytoplasmic tRNAHis -specific 5'-monophosphate methyltransferase.2018

    • Author(s)
      Tomita K & Liu Y.
    • Journal Title

      Front. Genet

      Volume: - Pages: 305-310

    • DOI

      10.3389/fgene.2018.00305

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular basis for nucleotide selection by tRNA nucleotidyltransferase toxin from Mycobacterium tuberculosis2022

    • Author(s)
      Jun Liu, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
    • Organizer
      RNAフロンティアミーティング2021 (20220303-0304 恩納村, 沖縄
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mechanistic insights into tRNA cleavage by a contact-dependent growth inhibitor protein and translation factors2022

    • Author(s)
      Jing Wang, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
    • Organizer
      RNAフロンティアミーティング2021 (20220303-0304 恩納村, 沖縄
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mechanistic insight into the m6A modification of RNA by METT-10 from Caenorhabditis elegans2022

    • Author(s)
      Jue Ju, Tomohiko Aoyama, Hidehito Kuroyanagi, Kozo Tomita
    • Organizer
      RNAフロンティアミーティング2021 (20220303-0304 恩納村, 沖縄
    • Related Report
      2021 Annual Research Report
  • [Presentation] Structural and biochemical study of C. elegans METT-102021

    • Author(s)
      Jue Ju, Tomohiko Aoyama, Hidehito Kuroyanagi, Kozo Tomita
    • Organizer
      第22回日本RNA学会年会 (20210707-0709 鶴岡、山形)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mechanistic analysis of specific tRNA cleavage by the CdiA-CT toxin from enterohemorrhagic Escherichia coli cells2021

    • Author(s)
      Jing Wang, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
    • Organizer
      第22回日本RNA学会年会 (20210707-0709 鶴岡、山形)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mechanism of the selective aminoacyl-tRNA acetylation by TacT from Salmonella Typhimurium2021

    • Author(s)
      Yuka Yashiro, Chuqiao Zhang, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
    • Organizer
      第22回日本RNA学会年会 (20210707-0709 鶴岡、山形)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Crystal structure of the Lin28-interacting module of human terminal uridylyltransferase that regulates let-7 expression2019

    • Author(s)
      山下征輔、富田 耕造
    • Organizer
      日本RNA学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] METTL16 の脊椎動物保存領域はU6 snRNA のm6A 修飾を促進する 第21回 日本RNA学会年2019

    • Author(s)
      青山智彦、山下征輔、富田 耕造
    • Organizer
      日本RNA学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Crystal Structure of the Enterohemorrhagic Escherichia coli AtaT-AtaR ToxinAntitoxin Complex2019

    • Author(s)
      八代悠歌、富田 耕造
    • Organizer
      日本RNA学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸管出血性大腸菌におけるAtaT-AtaRトキシン-アンチトキシン複合体の立体構造の決定2018

    • Author(s)
      八代悠歌、富田 耕造
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトTUT4によるLin28依存的なlet7 miRNA抑制の分子構造基盤2018

    • Author(s)
      山下征輔、富田 耕造
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Crystal structure of enterohemorrhagic Escherichia coli AtaT-AtaR toxin-antitoxin complex2018

    • Author(s)
      Yuka Yashiro & Kozo Tomita
    • Organizer
      27th tRNA Conference (2018 9.23-27, Strasbourg, France)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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