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Molecular mechanism of functional conversion from noncoding to coding RNAs

Research Project

Project/Area Number 22K19293
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 InstitutionOsaka University

Principal Investigator

Hirose Tetsuro  大阪大学, 大学院生命機能研究科, 教授 (30273220)

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: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordslong noncoding RNA / mRNA / 核外輸送 / サテライトDNA / 相分離 / noncoding RNA / nuclear export / satellite DNA / bimolecular condensate / ノンコーディングRNA / RNA顆粒 / 翻訳 / リピート配列
Outline of Research at the Start

細胞核内での確固とした機能を果たしているlncRNAが、温度変化の時系列に沿って細胞質に局在変化し、それに伴ってmRNAに機能転換して翻訳されるようになる新たな現象を見出した。本研究では、このlncRNAからmRNAへの機能転換機構を理解するために、その要となるlncRNAの核から細胞質への局在変化の分子機構を解明し、それが温度変化の時系列に沿ってどのように制御されているかを明らかにする。

Outline of Final Research Achievements

We analyzed the process by which HSATIII RNAs, which possess definitive lncRNA functions within the cell nucleus, relocate to the cytoplasm and convert its function to mRNA in response to thermal stress and recovery. Regarding the nuclear export of HSATIII RNA, we found that HSATIII RNA-binding proteins are remodeled and eventually the nuclear export factor ALY/REF binds to HSATIII RNA. This reassembly is promoted by the 'crucible' or 'sponge' functions of HSATIII. Next, stress granule factors and chaperones were detected as interactors of the HSATIII translation products. Furthermore, we confirmed that the translation products co-localize with these interactors at actin polymerization sites at the cell periphery.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、核から細胞質へのRNAの局在変化機構について、相分離構造体でのRNA機能が結合因子の再構築を促し、結果的に核外輸送因子を呼び込んでRNAを細胞質に輸送させるという流れが明らかになった。一方で、細胞質での翻訳産物の相互作用因子と細胞内局在が明らかになったことによって、機能転換したmRNAが機能的なポリペプチドを産生していることが示唆された。これによって、lncRNAからmRNAへの機能変換の全体像を把握し、前例のないRNAの複雑な一生を明らかにする道筋を整備できた。今後、このポリペプチド機能の解明によって、ストレス応答や関係する疾患の新たな機構解明につながる可能性が期待できる。

Report

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

    (35 results)

All 2024 2023 2022 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (22 results) (of which Int'l Joint Research: 2 results,  Invited: 11 results) Book (4 results)

  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Univ. Western Australia(オーストラリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Functional domains of nuclear long noncoding RNAs: Insights into gene regulation and intracellular architecture2023

    • Author(s)
      Obuse Chikashi、Hirose Tetsuro
    • Journal Title

      Current Opinion in Cell Biology

      Volume: 85 Pages: 102250-102250

    • DOI

      10.1016/j.ceb.2023.102250

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Satellite RNAs: emerging players in subnuclear architecture and gene regulation2023

    • Author(s)
      Ninomiya Kensuke、Yamazaki Tomohiro、Hirose Tetsuro
    • Journal Title

      The EMBO Journal

      Volume: 42 Issue: 18

    • DOI

      10.15252/embj.2023114331

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as distinct membraneless organelles2023

    • Author(s)
      Takakuwa Hiro、Yamazaki Tomohiro、Souquere Sylvie、Adachi Shungo、Yoshino Hyura、Fujiwara Naoko、Yamamoto Tetsuya、Natsume Tohru、Nakagawa Shinichi、Pierron Gerard、Hirose Tetsuro
    • Journal Title

      Nature Cell Biology

      Volume: 25 Issue: 11 Pages: 1664-1675

    • DOI

      10.1038/s41556-023-01254-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long non-coding RNAs: definitions, functions, challenges and recommendations2023

    • Author(s)
      Mattick John S.、Amaral Paulo P.、Carninci Piero、et al.
    • Journal Title

      Nature Reviews Molecular Cell Biology

      Volume: - Issue: 6 Pages: 430-447

    • DOI

      10.1038/s41580-022-00566-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A guide to membraneless organelles and their various roles in gene regulation2022

    • Author(s)
      Hirose Tetsuro、Ninomiya Kensuke、Nakagawa Shinichi、Yamazaki Tomohiro
    • Journal Title

      Nature Reviews Molecular Cell Biology

      Volume: 24 Issue: 4 Pages: 288-304

    • DOI

      10.1038/s41580-022-00558-8

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remarkable improvement in detection of readthrough downstream-of-gene transcripts by semi-extractable RNA-sequencing2022

    • Author(s)
      Iwakiri Junichi、Tanaka Kumiko、Chujo Takeshi、Takakuwa Hiro、Yamazaki Tomohiro、Terai Goro、Asai Kiyoshi、Hirose Tetsuro
    • Journal Title

      RNA

      Volume: 29 Issue: 2 Pages: 170-177

    • DOI

      10.1261/rna.079469.122

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] 非コードRNAによる相分離構造体の構築と機能制御2024

    • Author(s)
      廣瀬哲郎
    • Organizer
      The 3rd Kansai RNA Club
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 非コードRNAによる総分離構造体の構築と機能制御2024

    • Author(s)
      廣瀬哲郎
    • Organizer
      第2回タンパク質シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Short-tandem repeat型RNAであるHSATIIIの多彩な分子機能2023

    • Author(s)
      二宮賢介, 足達俊吾, 廣瀬哲郎
    • Organizer
      RNAフロンティアミーティング
    • Related Report
      2023 Annual Research Report
  • [Presentation] Characterization and functional analysis of HSATIII-derived repetitive proteins2023

    • Author(s)
      Kensuke Ninomiya, Shungo Adachi, Tetsuro Hirose
    • Organizer
      第24回日本RNA学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Exploring the Role of Architectural Long Noncoding RNAs in Shaping and Regulating Phase-Separated Cellular bodies2023

    • Author(s)
      Tetsuro HIROSE
    • Organizer
      50 Years Shine-Dalgarno Symposium
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Microphase Separation and Paraspeckles2023

    • Author(s)
      Tetsuro Hirose
    • Organizer
      Keystone Symposia
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Construction mechanism of nuclear paraspeckle as an isolated RNP micell2022

    • Author(s)
      Tetsuro Hirose
    • Organizer
      EMBO | EMBL Symposia: Cellular Mechanisms Driven by Liquid Phase Separation
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulatory Mechanisms of Intracellular Organization and Gene Expression by Noncoding RNAs2022

    • Author(s)
      廣瀬哲郎
    • Organizer
      千里ライフサイエンス振興財団セミナー
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] The dynamics and functions of cytoplasmic HSATIII lncRNAs2022

    • Author(s)
      Kensuke Ninomiya, Tetsuro Hirose
    • Organizer
      第23回日本RNA学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Searching for regulatory proteins for temperature-dependent recruitment of CLK1 to nuclear stress bodies2022

    • Author(s)
      Tsuyoshi Ueno, Shungo Adachi, Kensuke Ninomiya, Tetsuro Hirose
    • Organizer
      第23回日本RNA学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Combinations of repeat sequences in HSATIII lncRNAs dictate nSB subclasses2022

    • Author(s)
      Manami Kakuno, Kensuke Ninomiya, Junichi Iwakiri, Kiyoshi Asai, Tetsuro Hirose
    • Organizer
      第23回日本RNA学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Regulatory Mechanisms of Intracellular Organization by Noncoding RNAs2022

    • Author(s)
      廣瀬哲郎
    • Organizer
      RNAインフォマティクス道場
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Regulatory mechanisms of intracellular organization and gene expression by noncoding RNAs2022

    • Author(s)
      廣瀬哲郎
    • Organizer
      立命館大国際稀少疾患シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Construction mechanism of nuclear paraspeckle as an isolated RNP micell2022

    • Author(s)
      廣瀬 哲郎, 高桑 央, 山本 哲也, 山崎 智弘
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] CLK1の温度依存的な核内ストレス体への リクルートを担う制御タンパク質の同定2022

    • Author(s)
      上野 剛志, 足達 俊吾, 二宮 賢介, 廣瀬 哲郎
    • Organizer
      RNAフロンティアミーティング2022
    • Related Report
      2022 Research-status Report
  • [Presentation] HSATIII lncRNAのリピート配列パターン抽出による 核内ストレス体の再構成の試み2022

    • Author(s)
      角野 愛美, 二宮 賢介, 岩切 淳一, 松田優一, 浅井 潔, 廣瀬 哲郎
    • Organizer
      RNAフロンティアミーティング2022
    • Related Report
      2022 Research-status Report
  • [Presentation] Intracellular Architecture by Noncoding RNAs2022

    • Author(s)
      Tetsuro Hirose
    • Organizer
      Academia Sinica IBMS seminar
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 非コードRNAを足場に形成される核内相分離構造体におけるRNA結合タンパク質の役割2022

    • Author(s)
      廣瀬哲郎, 山崎智弘, 二宮賢介
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 構成的手法を用いた核内ストレス体の形成機構の解析2022

    • Author(s)
      岩田瑞季, 山崎智弘, 上野 剛志, 二宮賢介,廣瀬哲郎
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] The multifunctionality of HSATIII lncRNAs and its control mechanisms2022

    • Author(s)
      二宮賢介, 足達俊吾, 廣瀬哲郎
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] CLK1の温度依存的な核内ストレス体へのリクルートを担う 制御タンパク質の同定と解析2022

    • Author(s)
      上野 剛志, 足達 俊吾, 二宮 賢介, 廣瀬 哲郎
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒトゲノム完全配列から読み解くHSATIII lncRNAの配列パターン抽出とその人工化による核内ストレス体再構成の試み2022

    • Author(s)
      角野 愛美, 二宮 賢介, 岩切 淳一, 浅井 潔, 廣瀬 哲郎
    • 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 risks2023

    • Author(s)
      Hiro Takakuwa, Tomohiro Yamazaki, Tetsuro Hirose
    • Total Pages
      318
    • Publisher
      Springer
    • Related Report
      2023 Annual Research Report
  • [Book] 細胞 2022年7月号 Architectural RNAと液-液相分離(ArcRNAとストレス応答)2022

    • Author(s)
      二宮賢介, 廣瀬哲郎
    • Total Pages
      62
    • Publisher
      ニューサイエンス社
    • Related Report
      2022 Research-status Report
  • [Book] 細胞 2022年7月号 Architectural RNAと液-液相分離(総論 細胞内構造の足場としてのRNAの役割)2022

    • Author(s)
      廣瀬哲郎
    • Total Pages
      62
    • Publisher
      ニューサイエンス社
    • Related Report
      2022 Research-status Report
  • [Book] セントラルドグマの新常識(第3章 RNAの新常識 6.細胞内構造体の骨格として働くRNA)2022

    • Author(s)
      廣瀬哲郎, 山崎智弘, 山本哲也
    • Total Pages
      264
    • Publisher
      羊土社
    • ISBN
      9784758104043
    • Related Report
      2022 Research-status Report

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

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