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Functional analysis of liquid droplet formed by coupling of specific RNA binding proteins and a basal transcription machinery

Research Project

Project/Area Number 18K06063
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43010:Molecular biology-related
Research InstitutionYokohama City University

Principal Investigator

Kokubo Tetsuro  横浜市立大学, 生命医科学研究科, 教授 (10271587)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords転写調節 / 転写因子 / 局所翻訳制御 / SAGA / TFIID / TAF / TBP / 出芽酵母 / 基本転写因子 / RNA結合タンパク質 / 液-液相転移
Outline of Final Research Achievements

Genetic analysis revealed that (1) overexpression of Mpt5 had a growth inhibitory effect specifically in the taf1-deltaTAND strain, (2) overexpression of Mpt5[5A mutant] and Ssd1 had a growth inhibitory effect in the presence or absence of TAND, and (3) the growth inhibitory effect of Mpt5 overexpression was significantly increased in the ssd1-d strain. These results suggest that the synthetic lethality of the delta-RAM ssd1-d taf1-deltaTAND triple mutant strain is due to the up-regulation of Mpt5 function. RNA-seq analysis also provided clues to elucidate the cause of synthetic lethality in this triple mutant strain from the aspect of gene expression profiles.

Academic Significance and Societal Importance of the Research Achievements

CLN2に関する詳細な解析から、TANDはTFIID/SAGAによる転写バランスを制御すると考えられてきたが、これまでゲノムワイドな知見がなく、その一般性については不明であった。今回、RAMシグナリングの下流に位置し、TAND依存的に産生されるmRNAを網羅的に同定できたことから、TFIID/SAGAによるmRNA運命決定機構を理解する上での貴重な手がかりが得られたものと考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (4 results)

  • [Int'l Joint Research] Linkoping University(スウェーデン)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University Health Network/University of Toronto/University of Windsor(カナダ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] The function of Spt3, a subunit of the SAGA complex, in <i>PGK1</i> transcription is restored only partially when reintroduced by plasmid into <i>taf1 spt3</i> double mutant yeast strains2020

    • Author(s)
      Iwami Ryo、Takai Naoki、Kokubo Tetsuro
    • Journal Title

      Genes & Genetic Systems

      Volume: 95 Issue: 3 Pages: 151-163

    • DOI

      10.1266/ggs.20-00004

    • NAID

      130007891317

    • ISSN
      1341-7568, 1880-5779
    • Year and Date
      2020-06-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.2020

    • Author(s)
      Koji Kasahara, Risa Nakayama, Yuh Shiwa, Yu Kanesaki, Taichiro Ishige, Hirofumi Yoshikawa, Tetsuro Kokubo
    • Journal Title

      PLoS Genetics

      Volume: 16(6) Issue: 6 Pages: e1008865-e1008865

    • DOI

      10.1371/journal.pgen.1008865

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.2020

    • Author(s)
      K. Kasahara, R. Nakayama, Y. Shiwa, Y. Kanesaki, T. Ishige, H. Yoshikawa, T. Kokubo
    • Journal Title

      PLoS Genetics

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The function of Spt3, a subunit of the SAGA complex, in PGK1 transcription was restored only partially when reintroduced by plasmid into taf1 spt3 double mutant yeast strains.2020

    • Author(s)
      R. Iwami, N. Takai, T. Kokubo
    • Journal Title

      Genes & Genetic Systems

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transcriptional activation is weakened when Taf1p N-terminal domain 1 is substituted with its <i>Drosophila</i> counterpart in yeast TFIID2019

    • Author(s)
      K. Kasahara, S. Takahata, T. Kokubo
    • Journal Title

      Genes & Genetic Systems

      Volume: 94 Issue: 1 Pages: 51-59

    • DOI

      10.1266/ggs.19-00001

    • NAID

      130007625028

    • ISSN
      1341-7568, 1880-5779
    • Year and Date
      2019-02-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple direct interactions of TBP with the MYC oncoprotein.2019

    • Author(s)
      Y. Wei, D. Resetca, Z. Li, I. Johansson-Akhe, A. Ahlner, S. Helander, A. Wallenhammar,V. Morad, B. Raught, B. Wallner, T. Kokubo, Y. Tong, L. Z. Penn, M. Sunnerhagen
    • Journal Title

      Nat Struct Mol Biol.

      Volume: 26 Issue: 11 Pages: 1035-1043

    • DOI

      10.1038/s41594-019-0321-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ラパマイシンの標的分子FKBP12の出芽酵母における役割2019

    • Author(s)
      笠原浩司、中山理紗、志波優、兼崎友、石毛太一郎、吉川博文、古久保哲朗
    • Organizer
      第52回 酵母遺伝学フォーラム 研究報告会
    • Related Report
      2019 Research-status Report
  • [Presentation] p53活性化剤とCDK8阻害剤の併用は神経芽腫に対し細胞死を誘導する2018

    • Author(s)
      中島 綾奈、宮崎 允、日比谷 優子、富山 新太、古久保 哲朗、市村 幸一
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 出芽酵母においてSpt3/SAGAの一過的な機能喪失がもたらす解糖系遺伝子プロモーターのTaf1/TFIID依存的な転写活性化2018

    • Author(s)
      岩見 亮、高井 直樹、古久保 哲朗
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 出芽酵母のFK506/ラパマイシン結合タンパク質Fpr1は、リボソームタンパク質遺伝子の転写因子として働く2018

    • Author(s)
      笠原 浩司、中山 理紗、志波 優、兼崎 友、石毛 太一郎、吉川 博文、古久保 哲朗
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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