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Design of point mutations for gene regulation using RNA secondary structure

Research Project

Project/Area Number 18K18145
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 62010:Life, health and medical informatics-related
Research InstitutionThe University of Tokyo

Principal Investigator

Terai Goro  東京大学, 大学院新領域創成科学研究科, 特任准教授 (40785375)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords2次構造 / RNA / 点突然変異 / 原核生物 / 翻訳 / RNA2次構造 / 遺伝子発現 / 比較ゲノム / 配列設計 / 2次構造
Outline of Final Research Achievements

We analyzed large-scale data on mRNA sequences and protein expression levels in E. coli and extracted secondary structural features of mRNA that are highly correlated with protein expression levels. This feature was shown to have a higher correlation than existing secondary structural features such as minimum free energy. In addition, we improved this feature and developed an algorithm to learn it. We have also developed an algorithm to design mutations that positively or negatively regulate protein expression based on the discovered feature.

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現を人為的に制御する技術の開発は、学術的にも産業的にも重要である。本研究では、近年技術発展が著しいゲノムへの点突然変異を利用して、原核生物の遺伝子発現をプラスミド非依存的に制御する新しい情報技術を開発した。最近、大腸菌などの原核生物では開始コドン付近のmRNA 2次構造と、遺伝子の翻訳効率が強く関連することが示された。そこで、開始コドン付近の2次構造変化を引き起こすことで、翻訳効率を正あるいは負に制御できる点突然変異をデザインするアルゴリズムを開発した。この点突然変異による遺伝子制御は、面倒なゲノム改変や、外来性の発現調節因子なしで内在性遺伝子を個別に制御できるというメリットがある。

Report

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

    (3 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Improving the prediction accuracy of protein abundance in Escherichia coli using mRNA accessibility2020

    • Author(s)
      Terai Goro、Asai Kiyoshi
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 14 Pages: e81-e81

    • DOI

      10.1093/nar/gkaa481

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 大腸菌のタンパク質発現量予測のためのRNA2次構造特徴の抽出2020

    • Author(s)
      寺井悟朗、浅井潔
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Discovery of mRNA secondary structural features for the accurate prediction of protein abundance in Escherichia coli2020

    • Author(s)
      Goro Terai, Kiyoshi Asai
    • Organizer
      2020年日本バイオインフォマティクス学会年会
    • Related Report
      2020 Annual Research Report

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

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