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Analysis of the inhibition of mRNA surveillance

Research Project

Project/Area Number 21K19413
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionUniversity of the Ryukyus

Principal Investigator

YAMASHITA AKIO  琉球大学, 医学(系)研究科(研究院), 教授 (20405020)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsがん抗原 / フレームシフト変異 / mRNA分解 / ナンセンスコドン / 細胞ストレス応答 / mRNA翻訳 / mRNA監視機構
Outline of Research at the Start

がん免疫を賦活化する方法として、mRNA監視機構を抑制により、がん細胞に特異的ながん抗原の元となる異常タンパク質を強制発現させる手法の可能性が指摘されている。本研究では、mRNA監視機構を阻害する新たな手法の開発に向けて、mRNA監視機構の新規の阻害因子の同定と解析を目的とする。

Outline of Final Research Achievements

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that eliminates aberrant mRNAs containing premature termination codons (PTCs). Recent studies revealed that frame-shift mutation gene products encode tumor antigens. Since frame-sifted transcript containing PTCs, these mRNA degraded through NMD. We have newly established methods in which inhibit NMD via specific cellular stress. We also defined the requirement of newly synthesized protein for stress-mediated inhibition of NMD.

Academic Significance and Societal Importance of the Research Achievements

本研究で明らかとした、mRNA監視機構を阻害する複数の細胞ストレスは、これまで、NMDとの関わりがわかっていなかった。がん免疫療法による治療奏功は、フレームシフト変異の頻度と強く相関するが、NMDにより分解されるmRNAがコードする以上ペプチドがなぜ発現するのかについては謎のままである。本研究により、細胞ストレスによるNMD阻害が解明されたことにより、今後、免疫チェックポイント阻害剤の治療奏功予測が正確となるだけでなく、新たながん免疫賦活化薬の開発につながることが期待される。

Report

(2 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Deficiency of the kidney tubular angiotensin II type1 receptor?associated protein ATRAP exacerbates streptozotocin-induced diabetic glomerular injury via reducing protective macrophage polarization2022

    • Author(s)
      Haruhara Kotaro、Suzuki Toru、Wakui Hiromichi、Azushima Kengo、Kurotaki Daisuke、Kawase Wataru、Uneda Kazushi、Kobayashi Ryu、Ohki Kohji、Kinguchi Sho、Yamaji Takahiro、Kato Ikuma、Ohashi Kenichi、Yamashita Akio、Tamura Tomohiko、Tsuboi Nobuo、Yokoo Takashi、Tamura Kouichi
    • Journal Title

      Kidney International

      Volume: 101 Issue: 5 Pages: 912-928

    • DOI

      10.1016/j.kint.2022.01.031

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of tumor necrosis factor-α inhibition on kidney fibrosis and inflammation in a mouse model of aristolochic acid nephropathy2021

    • Author(s)
      Taguchi Shinya、Azushima Kengo、Yamaji Takahiro、Urate Shingo、Suzuki Toru、Abe Eriko、Tanaka Shohei、Tsukamoto Shunichiro、Kamimura Daisuke、Kinguchi Sho、Yamashita Akio、Wakui Hiromichi、Tamura Kouichi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 23587-23587

    • DOI

      10.1038/s41598-021-02864-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct RNA polymerase transcripts direct the assembly of phase-separated DBC1 nuclear bodies in different cell lines2021

    • Author(s)
      Mannen Taro、Goto Masato、Yoshizawa Takuya、Yamashita Akio、Hirose Tetsuro、Hayano Toshiya
    • Journal Title

      Molecular Biology of the Cell

      Volume: 32 Issue: 21

    • DOI

      10.1091/mbc.e21-02-0081

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue-specific expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in mouse models of chronic kidney disease2021

    • Author(s)
      Tsukamoto Shunichiro、Wakui Hiromichi、Azushima Kengo、Yamaji Takahiro、Urate Shingo、Suzuki Toru、Abe Eriko、Tanaka Shohei、Taguchi Shinya、Yamada Takayuki、Kinguchi Sho、Kamimura Daisuke、Yamashita Akio、Sano Daisuke、Nakano Masayuki、Hashimoto Tatsuo、Tamura Kouichi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 16843-16843

    • DOI

      10.1038/s41598-021-96294-8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] De novo ATP1A3 variants cause polymicrogyria2021

    • Author(s)
      Miyatake Satoko、Kato Mitsuhiro、Kumamoto Takuma、Hirose Tomonori、他
    • Journal Title

      Science Advances

      Volume: 7 Issue: 13 Pages: 2368-2368

    • DOI

      10.1126/sciadv.abd2368

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice2021

    • Author(s)
      Urate Shingo、Wakui Hiromichi、Azushima Kengo、Yamaji Takahiro、Suzuki Toru、Abe Eriko、Tanaka Shohei、Taguchi Shinya、Tsukamoto Shunichiro、Kinguchi Sho、Uneda Kazushi、Kanaoka Tomohiko、Atobe Yoshitoshi、Funakoshi Kengo、Yamashita Akio、Tamura Kouichi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 22 Pages: 12432-12432

    • DOI

      10.3390/ijms222212432

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] mRNA翻訳による生命現象制御の新展開2021

    • Author(s)
      山下 暁朗、藤原 俊伸
    • Organizer
      第44回 日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] mRNA監視機構制御因子SMG1キナーゼによる酸化ストレス応答制御機構2021

    • Author(s)
      山下 暁朗
    • Organizer
      第44回 日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Book] 疾患原因遺伝子・タンパク質の 解析技術と創薬/診断技術への応用~エピゲノム、トランスクリプトーム、マルチオミクス、オープンデータベースの利活用~2022

    • Author(s)
      藤本明洋ら 86人
    • Total Pages
      530
    • Publisher
      技術情報協会
    • ISBN
      9784861048777
    • Related Report
      2021 Research-status Report
  • [Remarks] 琉球大学 先進医療創成科学 山下暁朗 研究室

    • URL

      https://yamashita-lab.labby.jp/

    • Related Report
      2021 Research-status Report

URL: 

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

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