Study on noncoding RNA-dependent architecture of nuclear 3D structure

• Project/Area Number: 17H03630
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Hokkaido University
• Principal Investigator: Hirose Tetsuro 北海道大学, 遺伝子病制御研究所, 教授 (30273220)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: noncoding RNA / 相分離 / 核内構造体 / クロマチン / 遺伝子発現制御 / RNA / エピジェネティクス / クロマチン動態 / 核構造・機能 / 超分子複合体 / ノンコーディングRNA / タンパク質 / 遺伝子 / 核酸 / ゲノム / 細胞・組織 / 蛋白質 / 核内構造 / エピジェネティック制御

Outline of Final Research Achievements

Our research revealed that nuclear body paraspeckle is formed through intracellular phase separation induced by NEAT1 lncRNA and play significant function in formation of 3D chromatin structure. Meanwhile thermal stress induced nuclear stress bodies formed with HSATIII lncRNA serve as the scaffold of temperature dependent phosphorylation of specific regulators for the regulation of pre-mRNA splicing.

Academic Significance and Societal Importance of the Research Achievements

混み合った細胞核内において、クロマチン構造や転写後遺伝子発現制御を効率よくかつ精密に制御するために、相分離した核内構造体が様々な役割を果たしていることが明らかになった。特にこの相分離空間が特定のncRNAを骨格にして形成されていることによって、核内の特定部位にそのRNAに親和性のあるタンパク質因子を集約することができ、さらにはその制御因子を介してクロマチン高次構造を規定したり、制御因子の翻訳後修飾の場として働くことを明らかにし、未だ明確ではない核内における相分離環境の意義を明確に示すことができた。

Research Products

• [Int'l Joint Research] University of Western Australia(オーストラリア)
• [Int'l Joint Research] CNRS(フランス)
• [Int'l Joint Research] KAUST(サウジアラビア)
• [Int'l Joint Research] Francis Crick Institute(英国)
• [Int'l Joint Research] Max Planck Institute(ドイツ)
• [Int'l Joint Research] University of Western Australia(オーストラリア)
• [Int'l Joint Research] CNRS(フランス)
• [Int'l Joint Research] KAUST(サウジアラビア)
• [Int'l Joint Research] University of Western Australia(オーストラリア)
• [Int'l Joint Research] CNRS(フランス)
• [Int'l Joint Research] KAUST(サウジアラビア)
• [Int'l Joint Research] Francis Crick Institute(英国)
• [Int'l Joint Research] Helmholtz Zentrum(ドイツ)
• [Journal Article] Short Tandem Repeat-Enriched Architectural RNAs in Nuclear Bodies: Functions and Associated Diseases (2020)
  • Author(s): Ninomiya Kensuke、Hirose Tetsuro
  • Journal Title: Non-Coding RNA Volume: 6 Issue: 1 Pages: 6-6
  • DOI: 10.3390/ncrna6010006
  • Peer Reviewed / Open Access
• [Journal Article] Architectural RNAs for Membraneless Nuclear Body Formation (2020)
  • Author(s): Yamazaki T., Nakagawa S., Hirose T.
  • Journal Title: Cold Spring Harbor Symposia on Quantitative Biology Volume: LXXXIV Pages: 1-11
  • DOI: 10.1101/sqb.2019.84.039404
  • Peer Reviewed / Open Access
• [Journal Article] Forced isoform switching of Neat1_1 to Neat1_2 leads to the loss of Neat1_1 and the hyperformation of paraspeckles but does not affect the development and growth of mice (2019)
  • Author(s): Isobe Momo、Toya Hikaru、Mito Mari、Chiba Tomoki、Asahara Hiroshi、Hirose Tetsuro、Nakagawa Shinichi
  • Journal Title: RNA Volume: 26 Issue: 3 Pages: 251-264
  • DOI: 10.1261/rna.072587.119
  • Peer Reviewed / Open Access
• [Journal Article] LncRNA ‐dependent nuclear stress bodies promote intron retention through SR protein phosphorylation (2019)
  • Author(s): Ninomiya Kensuke、Adachi Shungo、Natsume Tohru、Iwakiri Junichi、Terai Goro、Asai Kiyoshi、Hirose Tetsuro
  • Journal Title: The EMBO Journal Volume: 39 Issue: 3
  • DOI: 10.15252/embj.2019102729
  • NAID: 120006876293
  • Peer Reviewed / Open Access
• [Journal Article] The long noncoding RNA NEAT1_1 is seemingly dispensable for normal tissue homeostasis and cancer cell growth (2019)
  • Author(s): Adriaens Carmen、Rambow Florian、Bervoets Greet、Silla Toomas、Mito Mari、Chiba Tomoki、Asahara Hiroshi、Hirose Tetsuro、Nakagawa Shinichi、Jensen Torben Heick、Marine Jean-Christophe
  • Journal Title: RNA Volume: 25 Issue: 12 Pages: 1681-1695
  • DOI: 10.1261/rna.071456.119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Two distinct nuclear stress bodies containing different sets of RNA-binding proteins are formed with HSATIII architectural noncoding RNAs upon thermal stress exposure (2019)
  • Author(s): Aly Mahmoud Khamis、Ninomiya Kensuke、Adachi Shungo、Natsume Tohru、Hirose Tetsuro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 516 Issue: 2 Pages: 419-423
  • DOI: 10.1016/j.bbrc.2019.06.061
  • NAID: 120006878349
  • Peer Reviewed
• [Journal Article] Cross-Regulation between TDP-43 and Paraspeckles Promotes Pluripotency-Differentiation Transition (2019)
  • Author(s): Modic Miha、Grosch Markus、Rot Gregor、Schirge Silvia、Lepko Tjasa、Yamazaki Tomohiro（中略）Hirose Tetsuro（20名中18番目）、Ule Jernej、Drukker Micha
  • Journal Title: Molecular Cell Volume: 74 Issue: 5 Pages: 951-965
  • DOI: 10.1016/j.molcel.2019.03.041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients. (2019)
  • Author(s): Gast M, Rauch B, Haghikia A, Nakagawa S, Haas J, Stroux A, Schmidt D, Schumann P, Weiss S, Jensen L, Kratzer A, Kraenkel N, Mller C, B;rnigen D, Hirose T, Blankenberg S, Escher F, Khl A, Kuss A, Meder B, Landmesser U, Zeller T, Poller W.
  • Journal Title: Cardiovasc Res. Volume: in press Issue: 13 Pages: 1886-1906
  • DOI: 10.1093/cvr/cvz085
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The expression of long noncoding RNA NEAT1 is reduced in schizophrenia and modulates oligodendrocytes transcription. (2019)
  • Author(s): Katsel P, Roussos P, Fam P, Khan S, Tan W, Hirose T, Nakagawa S, Pletnikov MV, Haroutunian V.
  • Journal Title: NPJ Schizophr. Volume: 5 Issue: 1 Pages: 3-3
  • DOI: 10.1038/s41537-019-0071-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed
• [Journal Article] Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. (2018)
  • Author(s): Ahmed ASI, Dong K, Liu J, Wen T, Yu L, Xu F, Kang X, Osman I, Hu G, Bunting KM, Crethers D, Gao H, Zhang W, Liu Y, Wen K, Agarwal G, Hirose T, Nakagawa S, Vazdarjanova A, Zhou J.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 115 Issue: 37
  • DOI: 10.1073/pnas.1803725115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation (2018)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Paraspeckles: Where Long Noncoding RNA Meets Phase Separation. (2017)
  • Author(s): Fox AH, Nakagawa S, Hirose T, Bond CS.
  • Journal Title: Trends Biochem Sci. Volume: 43(2) Issue: 2 Pages: 124-135
  • DOI: 10.1016/j.tibs.2017.12.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nuclear bodies built on architectural long noncoding RNAs: unifying principles of their construction and function (2017)
  • Author(s): Chujo T, Hirose T.
  • Journal Title: Mol Cells. Volume: 31;40(12) Pages: 889-896
  • Peer Reviewed
• [Journal Article] Neat1 is a p53-inducible lincRNA essential for transformation suppression. (2017)
  • Author(s): Mello SS, Sinow C, Raj N, Mazur PK, Bieging-Rolett K, Broz DK, Imam JFC, Vogel H, Wood LD, Sage J, Hirose T, Nakagawa S, Rinn J, Attardi LD.
  • Journal Title: Genes Dev. Volume: 31(11) Issue: 11 Pages: 1095-1108
  • DOI: 10.1101/gad.284661.116
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Unusual semi‐extractability as a hallmark of nuclear body‐associated architectural noncoding RNAs (2017)
  • Author(s): Chujo T, Yamazaki T, Kawaguchi T, Kurosaka S, Takumi T, Nakagawa S, Hirose T
  • Journal Title: The EMBO Journal Volume: - Issue: 10 Pages: 861-868
  • DOI: 10.15252/embj.201695848
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RNase Sensitivity Screening for Nuclear Bodies with RNA Scaffolds in Mammalian Cells (2017)
  • Author(s): Mannen, T. and Hirose, T.
  • Journal Title: Bio-protocol Volume: 7 Issue: 8
  • DOI: 10.21769/bioprotoc.2232
  • Peer Reviewed
• [Presentation] Formation of phase separated membrane-less nuclear bodies by long noncoding RNA (2019)
  • Author(s): Tetsuro Hirose
  • Organizer: EMBO workshop, RNP network dynamics in development and disease
  • Int'l Joint Research / Invited
• [Presentation] Architectural noncoding RNA controlling liquid-liquid phase separation (2019)
  • Author(s): Tetsuro Hirose
  • Organizer: 84th Cold Spring Harbor Laboratory Symposium on Quantitative Biology
  • Int'l Joint Research / Invited
• [Presentation] ノンコーディングRNAによる核内相分離構造体の形成機構 (2019)
  • Author(s): 廣瀬哲郎
  • Organizer: 第38回日本認知症学会学 術集会
  • Invited
• [Presentation] ノンコーディング RNA による相分離構造体の形成機構 (2019)
  • Author(s): 廣瀬哲郎
  • Organizer: 日本リウマチ学会 第6回JCRベーシックリサーチカンファレンス
  • Invited
• [Presentation] 細胞内の相分離構造体形成を主導する RNA の役割 (2019)
  • Author(s): 廣瀬哲郎
  • Organizer: 日本化学会秋季事業第9回 CSJ化学フェスタ2019
  • Invited
• [Presentation] Nuclear architecture by long noncoding RNAs through phase separation (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: China Nucleic Acids Forum 2018
  • Int'l Joint Research / Invited
• [Presentation] Nuclear body formation by long noncoding RNAs through phase separation (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: JAJ meeting 2018
  • Int'l Joint Research / Invited
• [Presentation] Formation and function of phase separated nuclear bodies with architectural noncoding RNAs (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: 第41回日本分子生物学会(ワークショップ)
  • Invited
• [Presentation] Ancient and Modern RNA Worlds (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: The 2nd GI-CoRE GSQ, GSB, & IGM Joint Symposium
  • Invited
• [Presentation] Molecular Mechanism of Nuclear Body Formation by Architectural Noncoding RNAs (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: SIL エキ スパートシンポジウム
  • Invited
• [Presentation] ノンコーディング RNA による細胞内構造構築 (2018)
  • Author(s): 廣瀬哲郎
  • Organizer: 第59回日本神経学会学術大会
  • Invited
• [Presentation] ノンコーディング RNA による細胞内構造構築 (2018)
  • Author(s): 廣瀬哲郎
  • Organizer: 第12回日本エピジェネティック研究 会
  • Invited
• [Presentation] Dissection of elements and machinery of architectural noncoding RNAs (2018)
  • Author(s): Tetsuro Hirose
  • Organizer: Keystone symposium Noncoding RNAs: Form, Function, Physiology
  • Int'l Joint Research / Invited
• [Presentation] 核内構造体アーキテクチュラルRNAの探索手法の開発：難溶性RNA-seqとFABS法 (2018)
  • Author(s): 中條岳志、田中くみ子、山崎智弘、萬年太郎、川口哲哉、黒坂哲、内匠透、中川真一、廣瀬哲郎
  • Organizer: 第3回北海道大学・部局横断シンポジウム
• [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回北海道大学・部局横断シンポジウム
• [Presentation] Dissection of NEAT1 lncRNA domains to establish distinct, highly ordered, phase-separated paraspeckle nuclear body (2018)
  • 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
  • Int'l Joint Research
• [Presentation] ノンコーディング RNAによる細胞内構造構築機構 (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 第69回日本細胞生物学会
  • Invited
• [Presentation] Molecular Dissection of Architectural Noncoding RNA Elements and Machinery (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 第43回内藤コンファレンス
  • Int'l Joint Research / Invited
• [Presentation] Nuclear Architecture by Long Noncoding RNAs (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 日韓(HU-KSMCB)ジョイントシンポジウム
  • Int'l Joint Research
• [Presentation] Noncoding RNA-dependent Nuclear Body Formation through Liquid-liquid Phase Separation (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 第40回日本神経科学会
  • Invited
• [Presentation] Molecular Dissection of Architectural Noncoding RNA Elements and Machinery, (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: Symposium on Multidisciplinary insights into higher order biological complexes
  • Int'l Joint Research / Invited
• [Presentation] Architectural Function of Noncoding RNA for Subcellular Structures (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 第40回日本分子生物学会（ConBio2017）
  • Int'l Joint Research
• [Presentation] Nuclear Architecture by Long Noncoding RNAs (2017)
  • Author(s): 廣瀬 哲郎
  • Organizer: 11th International Symposium on Nanomedicine (ISNM2017)
  • Int'l Joint Research / Invited
• [Presentation] The specific domains of architectural NEAT1 lncRNA induces the formation of the distinct phase-separated paraspeckle nuclear body (2017)
  • Author(s): Tomohiro Yamazaki, Taro Mannen, Sylvie Souquere, Hisanori Kiryu, Archa H. Fox, Shinichi Nakagawa, Gerard Pierron and Tetsuro Hirose
  • Organizer: RNA Society Meeting 2017
  • Int'l Joint Research
• [Presentation] Unusual semi-extractability as a hallmark of nuclear body-associated architectural long noncoding RNAs (2017)
  • Author(s): Takeshi Chujo, Tomohiro Yamazaki, Tetsuya Kawaguchi, Satoshi Kurosaka, Shinichi Nakagawa, and Tetsuro Hirose
  • Organizer: RNA Society Meeting 2017
  • Int'l Joint Research
• [Presentation] Unusual semi-extractability as a hallmark of nuclear body-associated architectural long noncoding RNAs (2017)
  • Author(s): Takeshi Chujo and Tetsuro Hirose
  • Organizer: 2nd International Symposium for Noncoding RNA Neo-Taxonomy in conjunction with Tokyo RNA Club 23rd Meeting
• [Presentation] The specific region of architectural NEAT1 lncRNA induces the formation of the phase-separated paraspeckle nuclear body (2017)
  • Author(s): Tomohiro Yamazakia, Taro Mannena, Sylvie Souquereb, Hisanori Kiryu, Archa H. Foxc,d, Shinichi Nakagawae, Gerard Pierronb and 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
  • Int'l Joint Research
• [Presentation] The specific regions of architectural NEAT1 lncRNA induce the formation of the phase-separated paraspeckle nuclear body (2017)
  • 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
• [Presentation] 核内構造体形成のアーキテクチュラル長鎖ncRNAの共通特性としての難抽出性 (2017)
  • Author(s): 中條岳志、山崎智弘、黒坂哲、内匠透、中川真一、廣瀬哲郎
  • Organizer: 第54回日本生化学会北海道支部例会
• [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
• [Presentation] Unusual semi-extractability as a hallmark of nuclear body-associated architectural long noncoding RNAs (2017)
  • Author(s): Takeshi Chujo, Tomohiro Yamazaki, Tetsuya Kawaguchi, Satoshi Kurosaka, Shinichi Nakagawa, and Tetsuro Hirose
  • Organizer: 第19回日本RNA学会年会
• [Presentation] 核内構造体パラスペックル内のNEAT1lncRNAの空間的配置を規定する分子メカニズムの解明 (2017)
  • Author(s): 吉野彪羅、山崎智弘、廣瀬哲郎
  • Organizer: 第19回日本RNA学会年会
• [Presentation] Molecular mechanisms to determine spatial organization of NEAT1 lncRNA within the paraspeckles (2017)
  • Author(s): Hyura Yoshino, Tomohiro Yamazaki, Tetsuro Hirose
  • Organizer: RNAフロンティアミーティング2017
• [Presentation] 核内構造体パラスペックルが独立した構造体として存在するための分子メカニズムの解明 (2017)
  • Author(s): 高桑 央、山崎 智弘、Sylvie Souquere、 Gerard Pierron、 廣瀬 哲郎
  • Organizer: RNAフロンティアミーティング2017
• [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: 第40回日本分子生物学会（ConBio2017）
• [Remarks] ノンコーディングRNA構造体nSBの新機能を発見～温度を感知したリン酸化反応の「るつぼ」として働く～
  • URL: https://www.hokudai.ac.jp/news/2019/12/rnansb.html
• [Remarks] ノンコーディング RNA の新暗号を解読 ~ゲノム機能に必要な新しい配列ルールの理解に貢献~
• [Remarks] プレスリリース「抽出しにくい RNA」から核内顆粒形成に関わる癌関連ノンコーディングRNAを発見
  • URL: https://www.hokudai.ac.jp/news/170413_pr.pdf
• [Remarks] 研究成果：「抽出しにくいRNA」から核内顆粒形成に関わる癌関連ノンコーディングRNAを発見
  • URL: http://www.igm.hokudai.ac.jp/achievements/20170413EMBO.php