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Development of the method for tRNA modomics

Research Project

Project/Area Number 17KT0054
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Complex Systems Disease Theory
Research InstitutionKumamoto University

Principal Investigator

Tomizawa Kazuhito  熊本大学, 大学院生命科学研究部(医), 教授 (40274287)

Project Period (FY) 2017-07-18 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordstRNA / ミトコンドリア病 / 糖尿病 / 修飾ヌクレオシド / モドミクス / オミクス / XLMR / tRNA修飾 / 質量分析 / RNA修飾 / 尿 / 生理学
Outline of Final Research Achievements

I studied to develop an inclusive and high throughput analysis method for tRNA modifications in urine and peripheral blood samples, and applied the method to diagnose mitochondrial disease and Asian-type diabetes. I succeeded to develop a analysis method by which we could detect more than 30 modified nucleosides within 1 h by LC/MS after removal of proteins form a small volume of urine and peripheral blood. I verified that we diagnosed mitochondrial disease by measuring two kinds of modified nucleosides in urine using the new analysis method. Moreover, this method was also useful for the diagnosis of Asian-type diabetes in patients who carry risk alleles in CDKAL1 gene.

Academic Significance and Societal Importance of the Research Achievements

現在、エピジェネティクスやメタボロミクスのようにセントラルドグマを制御する因子を網羅的に解析するオミックス研究は、生命現象を解明するだけでは無く、疾病発症や病態進行の予測、あるいはプレシジョン・メディシンへの期待から、全世界で熾烈な競争が行われている。本研究により、私はtRNA修飾を網羅的かつハイスループットに解析する技術開発に成功した。本成果により、tRNAモドミクスという新しいオミックス研究分野の開拓と既存のオミックス研究と統合することにより、次世代マルチオミックス研究への発展が期待できる。また、乳幼児に多く発症するミトコンドリア病の診断を非侵襲的にかつ簡易に診断できることが示せた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Int'l Joint Research] 南洋理工大学(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] パドバ大学(イタリア)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Regulation of growth hormone biosynthesis by Cdk5 regulatory subunit associated protein 1-like 1 (CDKAL1) in pituitary adenomas2019

    • Author(s)
      Takesue Y, Wei F-Y, Tomizawa K, Morioka M et al.,
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 9 Pages: 807-816

    • DOI

      10.1507/endocrj.EJ18-0536

    • NAID

      130007719407

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2-Methylthio Conversion of N6-Isopentenyladenosine in Mitochondrial tRNAs by CDK5RAP1 Promotes the Maintenance of Glioma-Initiating Cells2019

    • Author(s)
      Yamamoto Takahiro、Fujimura Atsushi、Wei Fan-Yan、Shinojima Naoki、Kuroda Jun-ichiro、Mukasa Akitake、Tomizawa Kazuhito
    • Journal Title

      iScience

      Volume: 21 Pages: 42-56

    • DOI

      10.1016/j.isci.2019.10.012

    • NAID

      120006816645

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex2019

    • Author(s)
      Naito Tomoki、Ercan Bilge、Krshnan Logesvaran、Triebl Alexander、Koh Dylan Hong Zheng、Wei Fan-Yan、Tomizawa Kazuhito、Torta Federico Tesio、Wenk Markus R、Saheki Yasunori
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.51401

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of mitochondrial iron homeostasis by sideroflexin 2.2019

    • Author(s)
      Mon EE, Wei FY, Ahmad RNR, Yamamoto T, Moroishi T, Tomizawa K.
    • Journal Title

      J Physiol Sci.

      Volume: 69 Issue: 2 Pages: 359-373

    • DOI

      10.1007/s12576-018-0652-2

    • NAID

      40021819064

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] tRNA modifications and islet function.2018

    • Author(s)
      Wei FY, Tomizawa K.
    • Journal Title

      Diabetes Obes Metab.

      Volume: Supple 2 Issue: S2 Pages: 20-27

    • DOI

      10.1111/dom.13405

    • Related Report
      2018 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] tRNAメチル化の恒常性2018

    • Author(s)
      富澤一仁
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Taurine-modification of mitochondrial tRNAs is essential for translation and controls proteostasis network via Opa12017

    • Author(s)
      Kazuhito Tomizawa
    • Organizer
      Cold Spring Harbor Asiaミーティング
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 難病「ミトコンドリア病」発症の原因解明~治療薬の開発に道筋~

    • URL

      http://www.kumamoto-u.ac.jp/whatsnew/seimei/20180110

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-07-21   Modified: 2021-02-19  

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