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Mechanisms for phase separation of RNA-induced nuclear bodies

Research Project

Project/Area Number 17K15058
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Molecular biology
Research InstitutionHokkaido University

Principal Investigator

Yamazaki Tomohiro  北海道大学, 遺伝子病制御研究所, 講師 (90732280)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords長鎖ノンコーディングRNA(lncRNA) / NEAT1 / 相分離 / 核内構造体 / 天然変性領域 / RNA結合タンパク質 / ヒト一倍体細胞 / CRISPR/Cas9 / Long noncoding RNA / 相転移 / パラスペックル / Low complexity domain / ヒト一倍体細胞株 / lncRNA / arcRNA
Outline of Final Research Achievements

Among long noncoding RNAs (lncRNAs) transcribed from vast majority of mammalian genomes, a class of them plays an essential role in construction of nuclear bodies. We analyzed paraspeckle nuclear body constructed by NEAT1 lncRNA as a model to investigate how the lncRNAs dictate their functions. We identified that several NEAT1 RNA domains determine NEAT1 stability, isoform switching, and paraspeckle formation through phase separation. Especially, the middle domain of NEAT1 has an essential role in the formation of phase-separated paraspeckle by interacting with partner RNA-binding proteins.

Academic Significance and Societal Importance of the Research Achievements

本研究により、癌関連ノンコーディングRNAであるNEAT1が核内構造体パラスペックルを作り上げるために必要なRNA領域の同定に成功した。具体的には、複数の機能ドメインが固有の機能を発揮することで構造体が作られることが明らかとなった。本研究成果は、癌を始めとする種々の疾患との関連が明らかになっているNEAT1の疾患における機能を詳細に理解する上で重要である。さらに今後、ノンコーディングRNA機能の体系的な理解に大きく寄与することや応用技術の開発などに繋がることが期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (29 results)

All 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (13 results) (of which Int'l Joint Research: 6 results) Book (2 results) Remarks (4 results)

  • [Int'l Joint Research] CNRS, Institut Gustave Roussy(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Western Australia(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Institut Gustave Roussy(France)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] University of Western Australia(Australia)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation2018

    • Author(s)
      Yamazaki Tomohiro、Souquere Sylvie、Chujo Takeshi、Kobelke Simon、Chong Yee Seng、Fox Archa H.、Bond Charles S.、Nakagawa Shinichi、Pierron Gerard、Hirose Tetsuro
    • Journal Title

      Molecular Cell

      Volume: 70 Issue: 6 Pages: 1038-1053

    • DOI

      10.1016/j.molcel.2018.05.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CRISPRa-mediated NEAT1 lncRNA upregulation induces formation of intact paraspeckles.2018

    • Author(s)
      Yamazaki T, Fujikawa C, Kubota A, Takahashi A, Hirose T.
    • Journal Title

      Biochemical and biophysical research communications

      Volume: 504 Issue: 1 Pages: 218-224

    • DOI

      10.1016/j.bbrc.2018.08.158

    • NAID

      120006725828

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular dissection of nuclear paraspeckles: towards understanding the emerging world of the RNP milieu.2018

    • Author(s)
      Nakagawa S, Yamazaki T, Hirose T.
    • Journal Title

      Open Biology

      Volume: 8 Issue: 10 Pages: 180150-180150

    • DOI

      10.1098/rsob.180150

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interactome analyses revealed that the U1 snRNP machinery overlaps extensively with the RNAP II machinery and contains multiple ALS/SMA-causative proteins2018

    • Author(s)
      Chi B, O’Connell JD, Yamazaki T, Gangopadhyay J, Gygi SP, Reed R
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8755-8766

    • DOI

      10.1038/s41598-018-27136-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 長鎖非コードRNAであるNEAT1の機能ドメインは相分離を介して核内構造体であるパラスペックルの形成をひき起こす2018

    • Author(s)
      山崎智弘、廣瀬哲郎
    • Journal Title

      First Author's

      Volume: - Pages: 070

    • DOI

      10.7875/first.author.2018.070

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Presentation] NEAT1 modular lncRNA domains dictate formation of phase-separated, distinct, highly ordered paraspeckle2019

    • Author(s)
      Tomohiro Yamazaki, Sylvie Souquere, Hyura Yoshino, Hiro Takakuwa, Takeshi Chujo, Archa H. Fox, Charles S. Bond, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
    • Organizer
      The 20th Takeda Science Foundation Symposium on Bioscience: RNA Neobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核内構造体パラスペックルはNEAT1 lncRNAの複数のモジュールドメインの協調した機能により構築される2018

    • Author(s)
      山崎 智弘、Sylvie Souquere、吉野 彪羅、高桑 央、中條 岳志、Archa H. Fox、Charles S. Bond、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Multiple NEAT1 modular RNA domains cooperatively construct phase-separated, distinct, highly ordered paraspeckle nuclear bodies2018

    • Author(s)
      Tomohiro Yamazaki, Souquere Sylvie, Hiro Takakuwa, Hyura Yoshino, Takeshi Chujo, Archa H. Fox, Charles S. Bond, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
    • Organizer
      JAJ RNA 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional domains of NEAT1 architectural lncRNA induce paraspeckle assembly through phase separation2018

    • Author(s)
      Tomohiro Yamazaki, Sylvie Souquere, Hyura Yoshino, Hiro Takakuwa, Takeshi Chujo, Archa H. Fox, Charles S. Bond, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
    • Organizer
      The 13th International Symposium of the Institute Network for Biomedical Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核内構造体パラスペックルはNEAT1 lncRNAの複数のモジュールドメインの協調した機能により構築される2018

    • Author(s)
      山崎 智弘、Sylvie Souquere、吉野 彪羅、高桑 央、中條 岳志、Archa H. Fox、Charles S. Bond、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      RNAフロンティアミーティング2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] NEAT1 lncRNA 機能ドメイン上での NONO オリゴマー化が相分離した核内構造体パラスぺックル形成を誘導する2018

    • Author(s)
      山崎 智弘、Sylvie Souquere、吉野 彪羅、高桑 央、中條 岳志、Archa H. Fox、Charles S. Bond、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      第 20 回日本 RNA 学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 核内構造体パラスペックルはNEAT1 lncRNAの複数の機能RNAドメインが協働することにより構築される2018

    • Author(s)
      山崎 智弘、Sylvie Souquere、吉野 彪羅、高桑 央、中條 岳志、Archa H. Fox、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      第3回北大部局横断シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Dissection of NEAT1 lncRNA domains to establish distinct, highly ordered, phase-separated paraspeckle nuclear body2018

    • Author(s)
      山崎 智弘、Sylvie Souquere、吉野 彪羅、高桑 央、木立 尚孝、Archa H. Fox、Charles S. Bond、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      Keystone symposium Noncoding RNAs: Form, Function, Physiology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The specific domains of architectural NEAT1 lncRNA induces the formation of the distinct phase-separated paraspeckle nuclear body2017

    • Author(s)
      Tomohiro Yamazaki, Taro Mannen, Sylvie Souquere, Hisanori Kiryu, Archa H. Fox, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
    • Organizer
      RNA2017 (The 22nd Annual Meeting of the RNA Society)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The specific region of architectural NEAT1 lncRNA induces the formation of the phase-separated paraspeckle nuclear body2017

    • Author(s)
      Tomohiro Yamazaki, Taro Mannen, Sylvie Souquere, Hisanori Kiryu, Archa H. Fox, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
    • Organizer
      第43回内藤コンファレンス 非コードRNA:生物学、化学、そして疾患
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The specific regions of architectural NEAT1 lncRNA induce the formation of the phase-separated paraspeckle nuclear body2017

    • Author(s)
      山崎 智弘、萬年 太郎、Sylvie Souquere、木立 尚孝、Archa H. Fox、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      第54回日本生化学会北海道支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] NEAT1長鎖ノンコーディングRNAは液相分離を誘導することで核内構造体パラスペックルを構築する2017

    • Author(s)
      山崎 智弘、Sylvie Souquere 、木立 尚孝、Archa H. Fox 、中川 真一、Gerard Pierron 、廣瀬 哲郎
    • Organizer
      第19回日本RNA学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 核内構造体パラスペックルはNEAT1 lncRNAの複数の機能ドメインにより構築される2017

    • Author(s)
      山崎 智弘、Sylvie Souquere、木立 尚孝、Archa H. Fox、中川 真一、Gerard Pierron、廣瀬 哲郎
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Book] Applied RNA Bioscience2018

    • Author(s)
      Seiji Masuda, Shingo Izawa, Sae Kato, Kei Kitahara, Takahiro Yamauchi, Naofumi Ito, Yuji Morita, Atsushi Ogawa, Kei Endo, Naoyuki Kataoka, Intisar Fouad Ali Mursi, Takayoshi Imai, Tomohiro Yamazaki, Eleonora Leucci, Yoshiya Ikawa, Jennifer Chu, Songling Bai, Yuhya Wakasa
    • Total Pages
      286
    • Publisher
      Springer
    • ISBN
      9789811083716
    • Related Report
      2018 Annual Research Report
  • [Book] Applied RNA Bioscience, Chapter 11, Long Noncoding RNAs and Their Applications:Focus on Architectural RNA (arcRNA), a Class of lncRNA2018

    • Author(s)
      Tomohiro Yamazaki
    • Total Pages
      286
    • Publisher
      Springer
    • ISBN
      9789811083716
    • Related Report
      2017 Research-status Report
  • [Remarks] 北海道大学遺伝子病制御研究所RNA生体機能分野

    • URL

      http://www.igm.hokudai.ac.jp/rna/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] ノンコーディングRNAネオタクソノミ

    • URL

      https://ncrna.jp/works/publication/item/391-neat1

    • Related Report
      2018 Annual Research Report
  • [Remarks] 北海道大学プレスリリース

    • URL

      https://www.hokudai.ac.jp/news/180622_pr2.pdf

    • Related Report
      2018 Annual Research Report
  • [Remarks] ライフサイエンス新着論文レビュー

    • URL

      http://first.lifesciencedb.jp/archives/18394

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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