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Neuronal activity-dependent translation regulation by the polyampholytic IDR of eIF3a

Research Project

Project/Area Number 22K19281
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionNational Institutes of Natural Sciences

Principal Investigator

Shiina Nobuyuki  大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 准教授 (30332175)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsRNA顆粒 / 天然変性領域 / IDR / eIF3a / 神経活動 / 流動性 / 局所翻訳 / 極性アミノ酸 / ダイナミクス / 局所的翻訳 / ポリアンフォライト
Outline of Research at the Start

ポリアンフォライトは陽・陰イオンから成るポリマーであり、その相互作用が生み出すゲルの物性は工業から生命科学の広い分野で注目されている。タンパク質のポリアンフォライトは液-液相分離を起こして凝縮体を形成する。本研究では、翻訳開始因子eIF3aのポリアンフォライト領域の改変が、神経活動依存的なeIF3a凝縮体の流動化、翻訳活性、ひいてはシナプス・記憶形成に与える影響をマウス脳神経で解析する。これにより、ポリアンフォライトのデザインルール・神経活動依存的スイッチング機構と生物機能を繋ぐ仕組みを明らかにする。この成果は、新たなスイッチ機能分子の開発等に応用できる可能性がある。

Outline of Final Research Achievements

During evolution, the eukaryotic translation initiation factor 3a (eIF3a) in vertebrates has acquired a long intrinsically disordered region (vIDR) of approximately 400 amino acids at its C-terminus. This vIDR suppresses the mobility of eIF3a within neuronal RNA granules and is involved in the regulation of local translation through activity-dependent increases in mobility. In this study, we analyzed the similarities and differences between the repeat sequence region in the first half of the vIDR (vIDR1) and the random sequence region in the second half of the vIDR (vIDR2). Contrary to our initial hypothesis that the function of the vIDR depends solely on its amino acid composition and length, and not on its sequence, our findings suggest that the differences between the repeat and random sequences in vIDR1 and vIDR2 are crucial.

Academic Significance and Societal Importance of the Research Achievements

天然変性領域(IDR)は、弱い相互作用を介して液-液相分離し、非膜オルガネラの形成やダイナミクスを制御する。しかし、IDRのアミノ配列は種間で保存性が低く、その配列の重要性については未解明な部分が多い。eIF3aのvIDR1とvIDR2は、アミノ酸組成は類似しているが、リピートとランダムという配列上の相違点がある。本研究で得られたこの2つの領域の配列の違いがvIDRの機能において重要であるという知見は、IDRの配列ルールの解明に向けて重要なものであり、大きな学術的意義を持つ。

Report

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

    (16 results)

All 2024 2023 2022 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 8 results) Presentation (5 results) (of which Invited: 2 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Piezoelectrically induced augmented functionality of primary cultured hippocampal neurons on electrospun PVDF-(Na, K) NbO3 composite fibers2024

    • Author(s)
      Deepak Khare、Kei Nakayama、Nobuyuki Shiina、Kenichi Kakimoto、Kumar Dubey Ashutosh
    • Journal Title

      Next Materials

      Volume: 2 Pages: 100070-100070

    • DOI

      10.1016/j.nxmate.2023.100070

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment2024

    • Author(s)
      Hideo Hagihara、Takao Keizo、他129名
    • Journal Title

      eLife

      Volume: 12 Pages: 89376-89376

    • DOI

      10.7554/elife.89376

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of RNG105/caprin1 dynamics by pathogenic cytoplasmic FUS and TDP-43 in neuronal RNA granules modulates synaptic loss2023

    • Author(s)
      Tomoyo Horio、Yui Ishikura、Rie Ohashi、Nobuyuki Shiina
    • Journal Title

      Heliyon

      Volume: 9 Issue: 6 Pages: e17065-e17065

    • DOI

      10.1016/j.heliyon.2023.e17065

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Protein Synthesis in the Lens2023

    • Author(s)
      椎名 伸之
    • Journal Title

      The Journal of The Japanese Society for Cataract Research

      Volume: 35 Issue: 1 Pages: 65-66

    • DOI

      10.14938/cataract.35-014

    • ISSN
      0915-4302, 2188-613X
    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] ILF3 prion-like domain regulates gene expression and fear memory under chronic stress2023

    • Author(s)
      Yamashita Akira、Shichino Yuichi、Fujii Kazuki、Koshidaka Yumie、Adachi Mayumi、Sasagawa Eri、Mito Mari、Nakagawa Shinichi、Iwasaki Shintaro、Takao Keizo、Shiina Nobuyuki
    • Journal Title

      iScience

      Volume: 26 Issue: 3 Pages: 106229-106229

    • DOI

      10.1016/j.isci.2023.106229

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Local translation and long-term memory formation regulated by neuronal RNA granules2022

    • Author(s)
      大橋 りえ、椎名 伸之
    • Journal Title

      生化学

      Volume: 94 Issue: 4 Pages: 529-536

    • DOI

      10.14952/SEIKAGAKU.2022.940529

    • ISSN
      0037-1017
    • Year and Date
      2022-08-25
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expanding evidence of fundamental regulation for biological processes by liquid–liquid phase separation2022

    • Author(s)
      椎名 伸之、奥野 浩行
    • Journal Title

      生化学

      Volume: 94 Issue: 4 Pages: 483-484

    • DOI

      10.14952/SEIKAGAKU.2022.940483

    • ISSN
      0037-1017
    • Year and Date
      2022-08-25
    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] Implications of RNG140(caprin2)-mediated translational regulation in eye lens differentiation2022

    • Author(s)
      中沢 香織、椎名 伸之
    • Journal Title

      The Journal of The Japanese Society for Cataract Research

      Volume: 34 Issue: 1 Pages: 83-83

    • DOI

      10.14938/cataract.34-018

    • ISSN
      0915-4302, 2188-613X
    • Related Report
      2022 Research-status Report
    • Open Access
  • [Presentation] 細胞質FUS/TLSとTDP-43による神経RNA顆粒RNG105の動態変化とシナプス損失2023

    • Author(s)
      椎名伸之
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Arf GEF mRNAの神経樹状突起局在制御がスパイン形成・成熟に与える影響2023

    • Author(s)
      大橋りえ, 藤井一希, 高雄啓三, 椎名伸之
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ILF3のプリオン様ドメインは慢性ストレス下で遺伝子発現と恐怖記憶を制御する2023

    • Author(s)
      山下映, 七野悠一, 藤井一希, 腰高由美恵, 安達真由美, 笹川恵理, 水戸麻里, 中川真一, 岩崎信太郎, 高雄啓三, 椎名伸之
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 水晶体分化におけるタンパク質合成制御2022

    • Author(s)
      椎名伸之
    • Organizer
      第61回日本白内障学会総会・第48回水晶体研究会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Arf GEF, GAPファミリーmRNAの神経樹状突起局在制御がシナプス形成に与える影響2022

    • Author(s)
      大橋りえ, 藤井一希, 高雄啓三, 椎名伸之
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Book] Phase Separation in Living Cells -Benefits and Risks-2023

    • Author(s)
      Nobuyuki Shiina (担当:分担執筆, 範囲:Regulation of Neuronal RNA Granule Dynamics Through Phase Separation in Memory Formation and Disease)
    • Total Pages
      303
    • Publisher
      Springer Singapore
    • Related Report
      2023 Annual Research Report
  • [Remarks] 神経変性疾患におけるシナプス損失の一因:RNA顆粒からのRNG105の解離

    • URL

      https://www.nibb.ac.jp/pressroom/news/2023/07/07.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] プリオン様ドメインがストレス下でもマウスの不快記憶形成を可能にすることを発見

    • URL

      https://www.nibb.ac.jp/pressroom/news/2023/03/30.html

    • Related Report
      2022 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2025-01-30  

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