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Deciphering the Wobble Hypothesis

Research Project

Project/Area Number 21K19363
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

TANAKA Motomasa  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (40321781)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords翻訳 / リボソーム / tRNA / コドン / プロファイリング / 揺らぎ塩基
Outline of Research at the Start

近年、同義置換によって翻訳速度が変わることで、合成最中のタンパク質のフォールディング構造や機能、ひいては高次機能まで変化しうることことが示唆されてきた。しかし、翻訳における揺らぎ仮説の実態は、その解析技術がなかったため、これまで十分に理解されていない。本研究では、揺らぎ塩基の詳細を調べるための実験系とバイオインフォマティクス解析のための技術基盤を確立することで、「揺らぎ仮説」の実態解明を目指す。

Outline of Final Research Achievements

In order to gain insights into wobble bases in mRNA translation, we have developed a novel simultaneous mRNA/tRNA ribosome profiling technique, This analytical method has allowed us to precisely analyze mRNA translation at single nucleotide resolution. We have applied this technique to a model mouse for neurodevelopmental diseases in which ribosome-associated quality control is dysregulated by lack of Ltn1, an E3 ligase. We found that in the Ltn1-deficneint brains the process of translation initiation is significantly compromised, which in turn impaired dendritic outgrowth and thereby led to manifestation of neurodevelopmental phenotypes.

Academic Significance and Societal Importance of the Research Achievements

DNAの遺伝情報がmRNAに転写されたあとに、どのようにしてリボソームがその遺伝情報をデコードし、タンパク質の合成に変換しているかを理解することは、あらゆる生命現象の根源に関わる。本研究で新たに開発する翻訳解析技術とバイオインフォマティクス解析手法は、疾患モデルの動物や細胞のおける翻訳解析に応用が可能であり、その疾患の病態解明や新たな治療法の開発につながる可能性がある。特に、どのような頻度、量の揺らぎ塩基が翻訳中のリボソームに取り込まれるかを明らかにすることは、翻訳過程の深い理解につながる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (7 results)

All 2023 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Dysregulation of ribosome-associated quality control elicits cognitive disorders via overaccumulation of TTC32023

    • Author(s)
      Endo R., Chen Y.K., Burke J., Takashima N., Suryawanshi N., Hui K.K., Miyazaki T., Tanaka M.
    • Journal Title

      Proc. Natl. Acad. Sci. U. S. A.

      Volume: 120

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Dysregulation of ribosome-associated quality control elicits neurodevelopmental disorders2023

    • Author(s)
      Motomasa Tanaka
    • Organizer
      GRC Mini Symposium, Academia Sinica
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activity-dependent Translatome Analysis Reveals Novel Protein Synthesis2023

    • Author(s)
      ayan Suryawanshi, Takayasu Mikuni, Motomasa Tanaka
    • Organizer
      A*STAR-RIKEN Joint Workshop, Singapore
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dysregulated Translation Rhythms of Synaptic Genes in Neuropsychiatric Disorders2023

    • Author(s)
      Motomasa Tanaka
    • Organizer
      GRC Translation Machinery in Health and Disease
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 神経疾患の鍵を握る細胞の“品質管理”

    • URL

      https://www.riken.jp/pr/closeup/2023/20230524_1/index.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] Making a bad situation worse

    • URL

      https://www.riken.jp/medialibrary/riken/pr/publications/riken_research/2023/rr202309.pdf

    • Related Report
      2023 Annual Research Report
  • [Remarks] タンパク質の品質管理

    • URL

      https://cbs2.riken.jp/magazine/06/#page=9

    • Related Report
      2023 Annual Research Report

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Published: 2021-07-13   Modified: 2025-01-30  

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