• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

RNA-based genetic switch using synthetic small molecular ligands that control RNA structure and function

Research Project

Project/Area Number 18H02107
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionOsaka University

Principal Investigator

DOHNO Chikara  大阪大学, 産業科学研究所, 准教授 (60420395)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywordsリボザイム / RNA分子糊 / RNA結合リガンド / 光スイッチ / RNAスイッチ / RNA高次構造
Outline of Final Research Achievements

We have developed an artificial RNA switch that can control the expression of a target protein by combining two of our key technologies, 1) synthetic RNA binding small molecular ligands that bind specifically to the target RNA and thereby induce the secondary and tertiary structure changes of the RNA (molecular glue for RNA), and 2) ribozyme whose structure and catalytic function is controlled by the molecular glue. We successfully created RNA switches that share the core operating system described above but exhibit different responses; OFF switch where gene expression levels are inhibited by the ligand, ON switch where expression levels are increased by the ligand, and ON/OFF reversibly switch where expression levels are controlled bidirectionally by light stimuli. These RNA switches are functional in human-cultured cell models.

Academic Significance and Societal Importance of the Research Achievements

本研究では、RNA結合小分子リガンドと外部刺激となる光を用いて、ヒト培養細胞内における標的タンパク質の発現を自在に制御可能な人工システムを構築した。標的遺伝子下流にRNAスイッチとなる配列を挿入することで動作するコンパクトな制御系であり、任意のタイミングで形質を発現するモデル細胞構築など合成生物学的意義が高い。本研究で採用し、実証したRNA結合小分子リガンドを基盤とする戦略は、RNA高次構造と機能を相関付けることのできる様々な機能性RNAに適用することができ、細胞機能の精密制御を通じた機能解明、創薬に資する分子作用機序の創出に貢献する。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (34 results)

All 2023 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 5 results) Presentation (17 results) (of which Int'l Joint Research: 11 results,  Invited: 5 results) Remarks (1 results)

  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ポーランド科学アカデミー生物有機化学研究所(ポーランド)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Premature translation termination mediated non-ER stress induced ATF6 activation by a ligand-dependent ribosomal frameshifting circuit2022

    • Author(s)
      Hsu Hsiu-Ting、Murata Asako、Dohno Chikara、Nakatani Kazuhiko、Chang KungYao
    • Journal Title

      Nucleic Acids Research

      Volume: 50 Issue: 9 Pages: 5369-5383

    • DOI

      10.1093/nar/gkac257

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Small molecule-induced trinucleotide repeat contractions during <i>in vitro</i> DNA synthesis2021

    • Author(s)
      Dohno Chikara、Hagihara Masaki、Binti Mohd Zaifuddin Nursakinah、Nihei Mizuki、Saito Kaoru、Nakatani Kazuhiko
    • Journal Title

      Chemical Communications

      Volume: 57 Issue: 26 Pages: 3235-3238

    • DOI

      10.1039/d1cc00349f

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rational design of a photoswitchable DNA glue enabling high regulatory function and supramolecular chirality transfer2021

    • Author(s)
      Simeth Nadja A.、Kobayashi Shotaro、Kobauri Piermichele、Crespi Stefano、Szymanski Wiktor、Nakatani Kazuhiko、Dohno Chikara、Feringa Ben L.
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 26 Pages: 9207-9220

    • DOI

      10.1039/d1sc02194j

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclic mismatch binding ligands interact with disease-associated CGG trinucleotide repeats in RNA and suppress their translation2021

    • Author(s)
      Konieczny Patryk、Mukherjee Sanjukta、Stepniak-Konieczna Ewa、Taylor Katarzyna、Niewiadomska Daria、Piasecka Agnieszka、Walczak Agnieszka、Baud Anna、Dohno Chikara、Nakatani Kazuhiko、Sobczak Krzysztof
    • Journal Title

      Nucleic Acids Research

      Volume: 49 Issue: 16 Pages: 9479-9495

    • DOI

      10.1093/nar/gkab669

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Short Tandem Repeat Contractions during In Vitro DNA Synthesis by Repeat-binding Molecules2021

    • Author(s)
      Hagihara Masaki、Dohno Chikara、Saito Kaoru、Sugimoto Kazuhiro、Hishinuma Yuta、Sohma Yuri、Shibata Tomonori、Nakatani Kazuhiko
    • Journal Title

      Chemistry Letters

      Volume: 50 Issue: 11 Pages: 1848-1851

    • DOI

      10.1246/cl.210415

    • NAID

      130008113718

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Naphthyridine Tetramer that Recognizes Tandem G-G Mismatches by Formation of Interhelical Complex2020

    • Author(s)
      Lu, Y. ; Dohno, C. ; Nakatani, K.
    • Journal Title

      Chem. Commun.

      Volume: 56 Issue: 5 Pages: 754-757

    • DOI

      10.1039/c9cc08111a

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assembly of ruthenium complexes on double strand DNA using mismatch binding ligand2020

    • Author(s)
      Ni, L. ; Yamada, T. ; Nakatani, K.
    • Journal Title

      Chem. Commun.

      Volume: 56 Issue: 1 Pages: 56-61

    • DOI

      10.1016/j.bbrc.2020.03.107

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The dimeric form of 1, 3 - diaminoisoquinoline derivative rescued the mis - splicing of Atp2a1 and Clcn1 genes in myotonic dystrophy type 1 mouse model2020

    • Author(s)
      Matsumoto, J. ; Nakamori, M. ; Okamoto, T. ; Murata, A. ; Dohno, C. ; Nakatani, K.
    • Journal Title

      Chem. Eur. J.

      Volume: 26 Issue: 63 Pages: 14305-14309

    • DOI

      10.1002/chem.202001572

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular glue for RNA: Regulating RNA structure and function through a synthetic RNA binding molecule2019

    • Author(s)
      Dohno, C.; Nakatani, K.
    • Journal Title

      ChemBioChem

      Volume: 20 Issue: 23 Pages: 2903-2910

    • DOI

      10.1002/cbic.201900223

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural insights into synthetic ligands targeting A?A pairs in disease-related CAG RNA repeats2019

    • Author(s)
      Mukherjee Sanjukta、Blaszczyk Leszek、Rypniewski Wojciech、Falschlunger Christoph、Micura Ronald、Murata Asako、Dohno Chikara、Nakatani Kazuhiko、Kiliszek Agnieszka
    • Journal Title

      Nucleic Acids Research

      Volume: 47 Issue: 20 Pages: 10906-10913

    • DOI

      10.1093/nar/gkz832

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Restoration of Ribozyme Tertiary Contact and Function by Using a Molecular Glue for RNA2018

    • Author(s)
      Dohno, C. ; Kimura, M. ; Nakatani, K.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 57 Issue: 2 Pages: 506-510

    • DOI

      10.1002/anie.201709041

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Dimeric 2,9‐Diamino‐1,10‐phenanthroline Derivative Improves Alternative Splicing in Myotonic Dystrophy Type 1 Cell and Mouse Models2018

    • Author(s)
      Li Jinxing、Nakamori Masayuki、Matsumoto Jun、Murata Asako、Dohno Chikara、Kiliszek Agnieszka、Taylor Katarzyna、Sobczak Krzysztof、Nakatani Kazuhiko
    • Journal Title

      Chemistry - A European Journal

      Volume: 24 Issue: 68 Pages: 18115-18122

    • DOI

      10.1002/chem.201804368

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] オルト位フッ素置換アゾベンゼンを有する新規光応答性核酸分子スイッチ2023

    • Author(s)
      梶原 優佳、堂野 主税、中谷 和彦
    • Organizer
      日本化学会第103春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] RNA反復配列を標的とした光応答性リガンドによる細胞内RNA fociの形成制御2023

    • Author(s)
      藤原 侑亮、柴田 知範、堂野 主税、中谷 和彦
    • Organizer
      日本化学会第103春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Control of RNA Foci Formation by Photo-Switchable Ligands2022

    • Author(s)
      Yusuke Fujiwara, Tomonori Shibata, Chikara Dohno, Kazuhiko Nakatani
    • Organizer
      ISNAC2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 直列連結したグアニン認識部位を有する新規核酸結合リガンドの合成と評価2021

    • Author(s)
      小柴 佑輔、堂野主税、中谷和彦
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Photoswitching of RNA structure and function by synthetic RNA binding ligands2021

    • Author(s)
      Chikara Dohno
    • Organizer
      The 24th SANKEN International Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 光異性化特性を向上させた新規光応答性核酸結合分子の開発2020

    • Author(s)
      小林笙太朗・堂野主税・中谷和彦
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Synthetic molecular switch to regulate DNA/RNA structures and functions2020

    • Author(s)
      Chikara Dohno
    • Organizer
      2nd Indo-Japan (NCBS/inStem-ISIR, Osaka University) Meeting: Interfacing Chemistry and Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Modulation of DNA/RNA structure and function by photoresponsive synthetic ligands2020

    • Author(s)
      Chikara Dohno
    • Organizer
      Osaka University - Groningen University Data Workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ピペラジン骨格を有する新規ナフチリジン誘導体の創成と RNA と の結合評価2019

    • Author(s)
      小林笙太朗, 廬 藝歡, 堂野主税, 中谷和彦
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Targeting RNA structure and function by synthetic RNA binding ligand2019

    • Author(s)
      Chikara Dohno
    • Organizer
      Indo-Japan (NCBS/inStem-ISIR, Osaka University) Meeting: Interfacing Chemistry and Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of RNA cleaving activity of hammerhead ribozyme by a synthetic RNA binding molecule2019

    • Author(s)
      Chikara Dohno, Maki Kimura, Kazuhiko Nakatani
    • Organizer
      The Commemorative International Symposium of the Japan Society of Nucleic Acids Chemistry (CISNAC 2019)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Modulation of ribozyme activity by conformational changes induced by a synthetic RNA binding molecule2019

    • Author(s)
      Chikara Dohno, Maki Kimura, Kazuhiko Nakatani
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA-based Genetic Switch Controlled by Synthetic RNA Binding Ligands2018

    • Author(s)
      Chikara Dohno
    • Organizer
      Asian 3 Roundtable on Nucleic Acids (A3RONA 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Recognition of DNA GGGGCC repeats by novel naphthyridine tetramer2018

    • Author(s)
      Yihuan Lu, Chikara Dohno, Kazuhiko Nakatani
    • Organizer
      International Symposium on Nucleic Acids Chemistry (ISNAC) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Rationally engineered ribozyme activatable by ligand induced restoration of tertiary structure2018

    • Author(s)
      Chikara Dohno, Maki Kimura, Kazuhiko Nakatani
    • Organizer
      International Symposium on Nucleic Acids Chemistry (ISNAC) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of Isoquinoline Ligand Binding to r(CUG) Repeats2018

    • Author(s)
      Jun Matsumoto, Jinxing Li, Masayuki Nakamori, Asako Murata, Chikara Dohno, Kazuhiko Nakatani
    • Organizer
      International Symposium on Nucleic Acids Chemistry (ISNAC) 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA結合分子によるRNA高次構造と機能の制御 (Small molecules that modulate RNA structures and functions)2018

    • Author(s)
      堂野主税
    • Organizer
      第三回 核酸を標的とした低分子創薬研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 産業科学研究所定例記者会見~合成分子でRNAの「形」と「機能」を制御する~

    • URL

      https://www.sanken.osaka-u.ac.jp/regular_press/teirei_89.pdf

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi