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Biosynthesis and function of characteristic RNA modifications found in human

Research Project

Project/Area Number 26702035
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Biomolecular chemistry
Research InstitutionThe 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) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordstRNA / 修飾酵素 / 生合成 / 遺伝子 / RNA修飾 / tRNA / 修飾 / 酵素
Outline of Final Research Achievements

We revealed the biogenesis and physiological function of 5-formylcytidien (f5C) modification specifically found in the wobble position of human/vertebrates mitochondrial tRNA-Met. A metabolic labeling analysis enables us to predict that f5C synthesis initiates methylation of C to 5-methylcitidine (m5C), and then oxidizes m5C to f5C. Actually, we successfully identified the methyltransferase NSUN3 and the oxygenase ALKBH1 and performed in vitro f5C reconstitution by using these enzymes. Knockout cells of each gene exhibited mitochondrial dysfunction and decreased mitochondrial translation in biochemical analyses. As for species-specific modifications other than f5C, in vitro reconstitution or modifying gene identification were achieved. To deeply understand the function of these modifications, further investigations will be required.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (36 results)

All 2018 2017 2016 2015 2014 Other

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease2018

    • Author(s)
      Asano Kana、Suzuki Takeo、Saito Ayaka、Wei Fan-Yan、Ikeuchi Yoshiho、Numata Tomoyuki、Tanaka Ryou、Yamane Yoshihisa、Yamamoto Takeshi、Goto Takanobu、Kishita Yoshihito、Murayama Kei、Ohtake Akira、Okazaki Yasushi、Tomizawa Kazuhito、Sakaguchi Yuriko、Suzuki Tsutomu
    • Journal Title

      Nucleic Acids Res.

      Volume: 46 Issue: 4 Pages: 1565-1583

    • DOI

      10.1093/nar/gky068

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defective Mitochondrial tRNA Taurine Modification Activates Global Proteostress and Leads to Mitochondrial Disease.2018

    • Author(s)
      Fakruddin M, Wei FY, Suzuki T, Asano K, Kaieda T, Omori A, Izumi R, Fujimura A, Kaitsuka T, Miyata K, Araki K, Oike Y, Scorrano L, Suzuki T, Tomizawa K.
    • Journal Title

      Cell Rep.

      Volume: 22 Issue: 2 Pages: 482-496

    • DOI

      10.1016/j.celrep.2017.12.051

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications2017

    • Author(s)
      Kawarada Layla、Suzuki Takeo、Ohira Takayuki、Hirata Shoji、Miyauchi Kenjyo、Suzuki Tsutomu
    • Journal Title

      Nucleic Acids Res.

      Volume: 45 Issue: 12 Pages: 7401-7415

    • DOI

      10.1093/nar/gkx354

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of 2-methylthio cyclic N6-threonylcarbamoyladenosine (ms2ct6A) as a novel RNA modification at position 37 of tRNAs2017

    • Author(s)
      Kang, B. I., Miyauchi, K., Matuszewski, M., D'Almeida, G. S., Rubio, M. A., Alfonzo, J. D., Inoue, K., Sakaguchi, Y., Suzuki, T., Sochacka, E., Suzuki, T.
    • Journal Title

      Nucleic Acids Res

      Volume: 45 Issue: 4 Pages: 2124-2136

    • DOI

      10.1093/nar/gkw1120

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met)2016

    • Author(s)
      Nakano, S., Suzuki, T., Kawarada, L., Iwata, H., Asano, K., Suzuki, T.
    • Journal Title

      Nat Chem Biol

      Volume: 12 Issue: 7 Pages: 546-51

    • DOI

      10.1038/nchembio.2099

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mtu1-mediated thiouridine formation of mitochondrial tRNAs is required for mitochondrial translation and is involved in reversible infantile liver injury2016

    • Author(s)
      Wu, Y., Wei, F. Y., Kawarada, L., Suzuki, T., Araki, K., Komohara, Y., Fujimura, A., Kaitsuka, T., Takeya, M., Oike, Y., Suzuki, T., Tomizawa, K.
    • Journal Title

      PLoS genetics

      Volume: 12 Issue: 9 Pages: e1006355-e1006355

    • DOI

      10.1371/journal.pgen.1006355

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A single methylation of 23S rRNA triggers late steps of 50S ribosomal subunit assembly2015

    • Author(s)
      Arai, T., Ishiguro, K., Kimura, S., Sakaguchi, Y., Suzuki, T. and Suzuki, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 112 Issue: 34

    • DOI

      10.1073/pnas.1506749112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans.2015

    • Author(s)
      Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, Takahashi N, Xie P, Michiue H, Fujimura A, Kaitsuka T, Matsui H, Koga Y, Mohri S, Suzuki T, Oike Y, Tomizawa K.
    • Journal Title

      Cell Metab

      Volume: 21 Issue: 3 Pages: 413-6

    • DOI

      10.1016/j.cmet.2015.01.019

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] RNAの修飾欠損と疾患2015

    • Author(s)
      鈴木 勉、浅野 奏、鈴木 健夫
    • Journal Title

      ファルマシア

      Volume: 51 Pages: 32-36

    • NAID

      130007447866

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18S rRNA2014

    • Author(s)
      Satoshi Ito, Sayuri Horikawa, Tateki Suzuki, Hiroki Kawauchi, Yoshikazu Tanaka, Takeo Suzuki, and Tsutomu Suzuki
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 289 Issue: 52 Pages: 35724-35730

    • DOI

      10.1074/jbc.c114.602698

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A single acetylation of 18S rRNA is essential for biogenesis of the small ribosomal subunit in Saccharomyces cerevisiae2014

    • Author(s)
      Ito, S., Akamatsu, Y., Noma, A., Kimura, S., Miyauchi, K., Ikeuchi, Y., Suzuki, T. and Suzuki, T
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 38 Pages: 26201-26212

    • DOI

      10.1074/jbc.m114.593996

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the CHTOP-Methylosome complex2014

    • Author(s)
      Hiroki Takai, Tetsu Akiyama et al.
    • Journal Title

      Cell Reports

      Volume: 9 Issue: 1 Pages: 48

    • DOI

      10.1016/j.celrep.2014.08.071

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs2014

    • Author(s)
      Suzuki T. and Suzuki T.
    • Journal Title

      Nucleic Acids Research

      Volume: (in press) Issue: 11 Pages: 7346-7357

    • DOI

      10.1093/nar/gku390

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ALKBH1 mediates 5-formylcytidine biogenesis in mammalian tRNAs2017

    • Author(s)
      Layla Kawarada, Takeo Suzuki, Tsutomu Suzuki
    • Organizer
      Conbio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Biogenesis and physiological role of 5-formylcytidine in mammalian mitochondrial tRNAMet2017

    • Author(s)
      Takeo Suzuki, Layla Kawarada, Saori Nakano, Takayuki Ohira, Hiroyoshi Iwata, Kana Asano, Shoji Hirata, Kenjyo Miyauchi, Tsutomu Suzuki
    • Organizer
      19th RNA meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Thermophilic archaeal tRNAs are stabilized by N4-acetylcyridine modification2017

    • Author(s)
      Ohira, T., Chen, M., Kurihashi, T., Yamauchi, R., Ito, S., Kaneko, A., Orita, I., Fukui, T., Suzuki, T., Yao, M., Tanaka, Y., Suzuki, T.
    • Organizer
      19th RNA meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] 哺乳類ミトコンドリアtRNAに存在する5-メチルシチジンの機能解析2017

    • Author(s)
      北川 翔 、中野 沙緒里、中川 真一、荒木 喜美、荒木 正健、鈴木 健夫、鈴木 勉
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] RNA-MSを用いたトリパノソーマmRNAおよびSL RNAにおける転写後修飾の解析2017

    • Author(s)
      穐近 慎一郎、松木 美知枝、鈴木 健夫、Ho Kiong、鈴木 勉
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] ALKBH1はミトコンドリアおよび細胞質tRNA修飾のジオキシゲナーゼとしてはたらく2017

    • Author(s)
      川原田 礼以良、鈴木 健夫、大平 高之、平田 翔児、宮内 健常、鈴木 勉
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mass spectrometric characterization of post-transcriptional modifications in mRNAs and spliced-leader RNA from Trypanosoma brucei2016

    • Author(s)
      Akichika, S., Matsuki, M., Suzuki, T., Ho, C. K., Suzuki, T.
    • Organizer
      MBSJ2016
    • Place of Presentation
      Pacifico Yokohama, Kanagawa, Japan
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Functional analysis of 5-methylcytidine in mammalian mitochondrial tRNA2016

    • Author(s)
      Kitagawa, S., Nakano, S., Nakagawa, S., Suzuki, T., Araki, K., Araki, M., Suzuki, T.
    • Organizer
      MBSJ2016
    • Place of Presentation
      Pacifico Yokohama, Kanagawa, Japan
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Substrate recognition by NSUN3, an RNA methyltransferase which initiates 5-formylcytidine formation in human mitochondrial tRNAMet2016

    • Author(s)
      In, S., Kawarada, L., Suzuki, T., Suzuki, T.
    • Organizer
      MBSJ2016
    • Place of Presentation
      Pacifico Yokohama, Kanagawa, Japan
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] NSUN3 initiates formation of 5-formylcytidine, a post-transcriptional modification in human mitochondrial tRNAMet required to decipher non-universal genetic code2016

    • Author(s)
      Nakano, S., Suzuki, T., Kawarada, L., Iwata, H., Asano, K., Suzuki, T.
    • Organizer
      RNA2016
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A complete landscape of post-transcriptional modifications in human mitochondrial tRNAs2016

    • Author(s)
      Suzuki, T., Yashiro, Y., Asano, K., Lin, H., Kirino, Y., Sakaguchi, Y., Suzuki, T.
    • Organizer
      RNA2016
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biogenesis and function of N6-methyladenosine in U snRNAs2016

    • Author(s)
      Ishigami, Y., Ohira, T., Akichika, S., Suzuki, T., Suzuki, T.
    • Organizer
      RNA2016
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] U snRNAにおけるN6-メチルアデノシン修飾の生合成と機能解析2015

    • Author(s)
      石神 宥真、大平 高之、穐近 慎一郎、鈴木 健夫、鈴木 勉
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド、神戸市、兵庫県
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Exploration and functional analysis of queuosine-glycosyltransferases in mammals2015

    • Author(s)
      Xuewei Zhao, Takeo Suzuki, Tsutomu Suzuki
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌、札幌市、北海道
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Biogenesis of 5-taurinomethyluridine in human mitochondrial tRNAs; implication for molecular pathogenesis of mitochondrial diseases2015

    • Author(s)
      Kana Asano, Takeo Suzuki, Fan-Yan Wei, Yoshiho Ikeuchi, Yuka Yashiro, Christin Tischner, Annette Hofer, Yoshihito Kishita, Yasushi Okazaki, Tina Wenz, Kazuhito Tomizawa, Tsutomu Suzuki
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌、札幌市、北海道
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Deficiency of tRNA modification causes the development of X-linked mental retardation2015

    • Author(s)
      Fan-Yan Wei, Yu Nagayoshi, Shoji Hirata, Takeo Suzuki, Tsutomu Suzuki, Kazuhito Tomizawa
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌、札幌市、北海道
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] ミトコンドリアtRNAタウリン修飾の生合成と機能2014

    • Author(s)
      鈴木 健夫、浅野 奏、魏 范研、富澤 一仁、池内 与志穂、鈴木 勉
    • Organizer
      第14回日本ミトコンドリア学会年会
    • Place of Presentation
      九大医 百年講堂、福岡市、福岡県
    • Year and Date
      2014-12-03 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 哺乳類ミトコンドリアにおけるtRNA48位の5-メチルシチジン修飾酵素の同定2014

    • Author(s)
      中野 紗緒里、鈴木 健夫、荒木 喜美、荒木 正健、鈴木 勉
    • Organizer
      第14回日本ミトコンドリア学会年会
    • Place of Presentation
      九大医 百年講堂、福岡市、福岡県
    • Year and Date
      2014-12-03 – 2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs2014

    • Author(s)
      Suzuki, T. and Suzuki, T.
    • Organizer
      The 25th tRNA conference
    • Place of Presentation
      Kyllini, Greece
    • Year and Date
      2014-09-21 – 2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mitochondrial disease as the first instance of RNA modopathy2014

    • Author(s)
      Takeo Suzuki, Kana Asano, Fan-Yan Wei, Kazuhito Tomizawa, Tsutomu Suzuki
    • Organizer
      第16回日本RNA学会年会
    • Place of Presentation
      ウインクあいち、名古屋市、愛知県
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analysis of the functional role of FTSJ1 related to non-syndromic X-linked intellectual disability2014

    • Author(s)
      Shoji Hirata, Takeshi Chujo, Takeo Suzuki, Kenjyo Miyauchi, Yuichi Goto, Tsutomu Suzuki
    • Organizer
      第16回日本RNA学会年会
    • Place of Presentation
      ウインクあいち、名古屋市、愛知県
    • Year and Date
      2014-07-23 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Remarks] 変則的な暗号を解読するためのはじめの一歩 ミトコンドリアゲノムの解読に必須なメチル化酵素を同定

    • URL

      http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/first-step-to-deciphering-a-non-universal-genetic-code.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] ヒトのミトコンドリアにおいて変則的な遺伝暗号の解読をつかさどる5-ホルミルシチジン修飾はNSUN3に

    • URL

      http://dx.doi.org/10.7875/first.author.2016.053

    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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