Function and dynamic regulation of animal specific RNA modifications

• Project/Area Number: 18H02094
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Takeo 東京大学, 大学院工学系研究科(工学部), 講師 (90533125)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: tRNA / 生合成 / デコーディング / RNA修飾 / アンチコドン / RNA / 修飾 / ミトコンドリア

Outline of Final Research Achievements

We determined modifying genes of queuosine derivatives found in the wobble position of some animal tRNAs. Knocking out each gene in cultured cells revealed the elevation of protein aggregates in cytoplasm, suggesting that the hypomodification of the modification by gene KO altered decoding ability of corresponding tRNA. To deeply understand the molecular and physiological function of these modifications, further investigations will be required.

Academic Significance and Societal Importance of the Research Achievements

RNA修飾のヒトや動物個体における機能は詳細が明らかでないものが多く、今回、修飾酵素の新たな特定を通じて、修飾機能の解明に迫った。特にコドン解読という、あらゆる生命に共通するプロセスにおいて当該修飾の特徴的な役割を提唱したことは一定の意義がある。また今回特定した遺伝子の中に、遺伝子異常が神経変性疾患と相関する例を見出しているため、病態の理解や疾患の診断や治療への応用が期待される。

Research Products

• [Journal Article] N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand (2021)
  • Author(s): Ogawa Akiko、Nagiri Chisae、Shihoya Wataru、Inoue Asuka、Kawakami Kouki、Hiratsuka Suzune、Aoki Junken、Ito Yasuhiro、Suzuki Takeo、Suzuki Tsutomu、Inoue Toshihiro、Nureki Osamu、Tanihara Hidenobu、Tomizawa Kazuhito、Wei Fan-Yan
  • Journal Title: Molecular Cell Volume: 81 Issue: 4 Pages: 674-674
  • DOI: 10.1016/j.molcel.2020.12.038
  • Peer Reviewed
• [Journal Article] Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability (2021)
  • Author(s): Nagayoshi Y.、Chujo T.、Hirata S.、Nakatsuka H.、Chen C.-W.、Takakura M.、Miyauchi K.、Ikeuchi Y.、Carlyle B. C.、Kitchen R. R.、Suzuki T.、Katsuoka F.、Yamamoto M.、Goto Y.、Tanaka M.、Natsume K.、Nairn A. C.、Suzuki T.、Tomizawa K.、Wei F.-Y.
  • Journal Title: Science Advances Volume: 7 Issue: 13
  • DOI: 10.1126/sciadv.abf3072
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complete chemical structures of human mitochondrial tRNAs (2020)
  • Author(s): Suzuki Takeo、Yashiro Yuka、Kikuchi Ittoku、Ishigami Yuma、Saito Hironori、Matsuzawa Ikuya、Okada Shunpei、Mito Mari、Iwasaki Shintaro、Ma Ding、Zhao Xuewei、Asano Kana、Lin Huan、Kirino Yohei、Sakaguchi Yuriko、Suzuki Tsutomu
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41467-020-18068-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mass Spectrometric Analysis of Mitochondrial RNA Modifications (2020)
  • Author(s): Ishigami Yuma、Suzuki Tsutomu、Suzuki Takeo
  • Journal Title: Methods in Molecular Biology Volume: 2192 Pages: 89-101
  • DOI: 10.1007/978-1-0716-0834-0_8
  • ISBN: 9781071608333, 9781071608340
  • Peer Reviewed
• [Journal Article] ミトコンドリアtRNA修飾とミトコンドリア病 (2020)
  • Author(s): 鈴木健夫
  • Journal Title: 遺伝子医学MOOK 35号 ミトコンドリアと病気 Volume: 35 Pages: 268-274
• [Journal Article] Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs (2019)
  • Author(s): Shinoda Saori、Kitagawa Sho、Nakagawa Shinichi、Wei Fan-Yan、Tomizawa Kazuhito、Araki Kimi、Araki Masatake、Suzuki Takeo、Suzuki Tsutomu
  • Journal Title: Nucleic Acids Research Volume: 47 Issue: 16 Pages: 8734-8745
  • DOI: 10.1093/nar/gkz575
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct Modified Nucleosides in tRNATrp from the Hyperthermophilic Archaeon Thermococcus kodakarensis and Requirement of tRNA m2G10/m22G10 Methyltransferase (Archaeal Trm11) for Survival at High Temperatures (2019)
  • Author(s): Hirata Akira、Suzuki Takeo、Nagano Tomoko、Fujii Daishiro、Okamoto Mizuki、Sora Manaka、Lowe Todd M.、Kanai Tamotsu、Atomi Haruyuki、Suzuki Tsutomu、Hori Hiroyuki
  • Journal Title: Journal of Bacteriology Volume: 201 Issue: 21 Pages: 1-17
  • DOI: 10.1128/jb.00448-19
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Higd1a improves respiratory function in the models of mitochondrial disorder (2019)
  • Author(s): Nagao Takemasa、Shintani Yasunori、Hayashi Takaharu、Kioka Hidetaka、Kato Hisakazu、Nishida Yuya、Yamazaki Satoru、Tsukamoto Osamu、Yashirogi Shohei、Yazawa Issei、Asano Yoshihiro、Shinzawa‐Itoh Kyoko、Imamura Hiromi、Suzuki Takeo、Suzuki Tsutomu、Goto Yu‐ichi、Takashima Seiji
  • Journal Title: The FASEB Journal Volume: 34 Issue: 1 Pages: 1859-1871
  • DOI: 10.1096/fj.201800389r
  • Peer Reviewed
• [Journal Article] Impact of intron removal from tRNA genes on Saccharomyces cerevisiae (2019)
  • Author(s): Hayashi Sachiko、Mori Shunsuke、Suzuki Takeo、Suzuki Tsutomu、Yoshihisa Tohru
  • Journal Title: Nucleic Acids Research Volume: - Issue: 11 Pages: 5936-5949
  • DOI: 10.1093/nar/gkz270
  • Peer Reviewed / Open Access
• [Journal Article] ヒドロキシル化 (2018)
  • Author(s): 鈴木, 健夫、鈴木, 勉
  • Journal Title: 生体の科学 Volume: 69 Pages: 389-399
• [Presentation] Biogenesis and Regulation of tRNA Modifications Associated with Human Diseases (2020)
  • Author(s): Takeo Suzuki
  • Organizer: 4th ETH Zurich - The University of Tokyo Strategic Partnership Symposium: Innovations in Chemical Biology
  • Int'l Joint Research / Invited
• [Presentation] Biogenesis and regulation of mitochondrial tRNA modifications associated with mitochondrial diseases (2019)
  • Author(s): Takeo Suzuki
  • Organizer: Joint meeting of the 16th Conference ASMRM and the 19th Conference J-mit
  • Int'l Joint Research / Invited
• [Presentation] Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs (2019)
  • Author(s): Shinoda, S., Kitagawa, S., Nakagawa, S., Wei, F. Y., Tomizawa, K., Araki, K., Araki, M., Suzuki, T., Suzuki, T.
  • Organizer: 21st RNA meeting
• [Presentation] Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase (2019)
  • Author(s): Akichika, S., Hirano, S., Shichino, Y., Suzuki, T., Nishimasu, H., Ishitani, R., Sugita, A., Hirose, Y., Iwasaki, S., Nureki, O., Suzuki, T.
  • Organizer: 20th Takeda Science Foundation Symposium on Bioscience, RNA Neobiology
  • Int'l Joint Research
• [Presentation] Identification and characterization of tRNA queuosine-glycosyltransferase in mammal (2019)
  • Author(s): Ma, D., Zhao, X., Suzuki, T., Suzuki, T.
  • Organizer: 20th Takeda Science Foundation Symposium on Bioscience, RNA Neobiology
  • Int'l Joint Research
• [Presentation] ミトコンドリアにおける暗号解読の担い手：tRNA修飾 (2018)
  • Author(s): 鈴木, 健夫
  • Organizer: 第18回日本ミトコンドリア学会年会
  • Invited
• [Presentation] ヒト疾患に関わるtRNAタウリン修飾の生合成と代謝制御 (2018)
  • Author(s): Suzuki, T., Asano, K., Saito, A., Wei, F. Y., Tomizawa, K., Sakaguchi, Y., Suzuki, T.
  • Organizer: 20th RNA meeting
• [Remarks] ヒトミトコンドリアtRNA修飾の全体像を解明―RNA修飾異常疾患の究明へ大きな前進
  • URL: https://www.t.u-tokyo.ac.jp/foe/press/setnws_202008311155455788959888.html