Boron nutrient mechanism of ribosome stalling via AUGUAA sequence

• Project/Area Number: 18K06278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44030:Plant molecular biology and physiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tanaka Mayuki 東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (80546292)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: リボソーム / ホウ素 / uORF / AUGUAA / mRNA分解 / ｍRNA分解 / 転写後制御 / シロイヌナズナ

Outline of Final Research Achievements

In this study, I aimed to reveal the mechanism of boron-dependent ribosomes sralilng on the non-amino acid coding sequence AUG-UAA, the initiation codon - stop codon in the 5' untranslated region. By combining structural analysis of ribosomes by cryo-electron microscopy with biochemical experiments, it was suggested that boron stabilizes the translation termination factor eRF1, which binds to the A site of ribosomes during translation termination step at the stop codon of AUG-UAA, and promotes peptide hydrolysis, thereby facilitating translation termination. In addition, I found factors involved in the regulation of NIP5;1 expression by screening analysis.

Academic Significance and Societal Importance of the Research Achievements

これまで、開始コドンと終止コドンしかない最小ORFはペプチドが無く、機能を持つとは考えられてこなかった。しかし、申請者の研究から、AUG-UAAを介したホウ素濃度依存的なリボソーム停滞による翻訳制御機構が明らかになった。この制御は、リボソームを停滞させ、翻訳を止める仕組みではなく、AUG-UAAでの翻訳を終結させるために、ホウ素が補助因子として関わっている、これまでにない新しい翻訳終結の仕組みであった。この発見は、タンパク質合成は実は翻訳終結の段階で様々な化合物によって制御されている可能性を示唆するものである。申請者の発見ははタンパク質の翻訳制御機構に新たな分野を拓いたと考えられる。

Research Products

• [Journal Article] Boron‐dependent regulation of translation through AUGUAA sequence in yeast (2020)
  • Author(s): Tsednee Munkhtsetseg、Tanaka Mayuki、Kasai Koji、Fujiwara Toru
  • Journal Title: Yeast Volume: 37 Issue: 12 Pages: 638-646
  • DOI: 10.1002/yea.3526
  • Peer Reviewed
• [Presentation] Structural analysis of boron-dependent ribosome stalling on the AUGUAA sequence (2021)
  • Author(s): Mayuki Tanaka, Takeshi Yokoyama, Madoka Nishimoto, Kengo Tsuda, Naoyuki Sotta, Hideki Shigematsu, Mikako Shirouzu, Takuhiro Ito, Toru Fujiwara
  • Organizer: 第62回植物生理学会
• [Presentation] Identification of genes involved in the regulation of NIP5;1 expression in response to boron in Arabidopsis thaliana (2020)
  • Author(s): Mayuki Tanaka, Naoyuki Sotta, Toru Fujiwara
  • Organizer: 第61回植物生理学会
• [Presentation] AUGUAA配列を介したNIP5;1mRNAのホウ素依存的翻訳制御に関与するシロイヌナズナ遺伝子の同定 (2020)
  • Author(s): 田中真幸、反田直之、藤原徹
  • Organizer: 土壌肥料学会2020年度岡山大会
• [Presentation] Identification of genes involved in the regulation of NIP5;1 expression in response to boron in Arabidopsis thaliana (2020)
  • Author(s): 田中真幸
  • Organizer: 第６１回植物生理学会