Gene regulation by using an ligand-responsive miRNA pathway

• Project/Area Number: 23710270
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: MURATA Asako 大阪大学, 産業科学研究所, 助教 (50557121)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: マイクロRNA / cell-basedセレクション / 低分子化合物 / cell-based セレクション

Research Abstract

This study aimed to explore an artificial miRNA pathway that can be regulated by small-molecule ligands. Ligand-binding sites were created in an endogenous pre-miRNA by partially randomizing the sequence. Construction of the expression vector containing the partially randomized pre-miRNA library and the optimization of conditions for cell-based selection were performed. Moreover, in vitro selection of RNA molecules that bind to a novel naphthyridine derivatives was performed.

Research Products

• [Journal Article] Fluorescent indicator displacement assay of ligands targeting 10 microRNA precursors (2013)
  • Author(s): Murata, A.; Harada, Y.; Fukuzumi, T.; Nakatani, K.
  • Journal Title: Bioorg. Med. Chem. Volume: 21 Issue: 22 Pages: 7101-7106
  • DOI: 10.1016/j.bmc.2013.09.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Xanthone derivatives as potential inhibitors of miRNA processing by human Dicer: Targeting secondary structures of pre-miRNA by small molecules. (2013)
  • Author(s): Asako Murata, Takeo Fukuzumi, Shiori Umemoto, Kazuhiko Nakatani
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23 Issue: 1 Pages: 252-255
  • DOI: 10.1016/j.bmcl.2012.10.108
  • Peer Reviewed
• [Journal Article] Ligand-inducible formation of RNA pseudoknot (2013)
  • Author(s): Matsumoto, S., Hong, C; Otabe, T.; Murata, A.; Nakatani, K.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 23 Issue: 12 Pages: 3539-3541
  • DOI: 10.1016/j.bmcl.2013.04.037
  • Peer Reviewed
• [Journal Article] Structure-activity studies on the fluorescent indicator in the displacement assay for the screening of small molecules binding to RNA. (2012)
  • Author(s): Shiori Umemoto, Seongwang Im, Jinhua Zhang, Masaki Hagihara, Asako Murata, Yasue Harada, Takeo Fukuzumi, Takahiro Wazaki, Shin-ichi Sasaoka, and Kazuhiko Nakatani
  • Journal Title: Chemistry A European Journal Volume: 18 Issue: 32 Pages: 9999-10008
  • DOI: 10.1002/chem.201103932
  • Peer Reviewed
• [Journal Article] Structure-activity studies on the fluorescent indicator in the displacement assay for the screening of small molecules binding to RNA (2012)
  • Author(s): Shiori Umemoto, Seongwang Im, Jinhua Zhang, Masaki Hagihara, Asako Murata, Yasue Harada, Takeo Fukuzumi, Takahiro Wazaki, Shin-ichi Sasaoka, and Kazuhiko Nakatani
  • Journal Title: Chemistry - A European Journal Volume: 18
  • Peer Reviewed
• [Presentation] RNAの構造・機能を制御する小分子化合物の開発 (2014)
  • Author(s): 村田亜沙子
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学(愛知県)
  • Year and Date: 2014-03-27
• [Presentation] RNAの構造・機能を制御する小分子化合物の開発 (2014)
  • Author(s): 村田亜沙子
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
  • Invited
• [Presentation] RNA結合性化合物を用いたマイクロRNA 前駆体プロセシングの調節 (2013)
  • Author(s): 村田亜沙子・福澄岳雄・梅本詩織・神山いづみ・堂野主税・中谷和彦
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学(滋賀県)
  • Year and Date: 2013-03-23
• [Presentation] Targeting secondary structures of pre-miRNA by small molecules : Development of potential inhibitors of pre-miRNA processing (2013)
  • Author(s): Murata , A.; Sugai, A.; Fukuzumi, T.; Umemoto, S.; Dohno, C.; Nakatani, K.
  • Organizer: RNA 2013, the 18th Annual Meeting of the RNA Society
  • Place of Presentation: Congress Center Davos (Switzerland)
• [Presentation] Targeting secondary structures of pre-miRNA by small molecules : Development of potential inhibitors of pre-miRNA processing (2013)
  • Author(s): Asako Murata, Ayako Sugai, Takeo Fukuzumi, Shiori Umemoto, Chikara Dohno, Kazuhiko Nakatani
  • Organizer: RNA 2013, the 18th Annual Meeting of the RNA Society
  • Place of Presentation: Congress Center Davos (Davos, Switzerland)
• [Presentation] Suppression of miR-29a maturation by ligand binding (2013)
  • Author(s): Takahiro Otabe, Asako Murata, Fumie Takei, Kazuhiko Nakatani
  • Organizer: RNA 2013, the 18th Annual Meeting of the RNA Society
  • Place of Presentation: Congress Center Davos (Davos, Switzerland)
• [Presentation] Translational regulation by ligand-inducible formation of RNA pseudoknot (2013)
  • Author(s): Saki Matsumoto, Changfeng Hong, Asako Murata, Kazuhiko Nakatani
  • Organizer: RNA 2013, the 18th Annual Meeting of the RNA Society
  • Place of Presentation: Congress Center Davos (Davos, Switzerland)
• [Presentation] Synthesis of the restrained naphthyridine dimer and the exploration for binding RNA by in vitro selection (2013)
  • Author(s): Yue Di, Takahiro Otabe, Jinxing Li, Asako Murata, Kazuhiko Nakatani
  • Organizer: ISNAC2013
  • Place of Presentation: 神奈川大学（神奈川県横浜市）
• [Presentation] RNA結合性化合物を用いたマイクロRNA前駆体プロセシングの調節 (2013)
  • Author(s): 村田亜沙子・福澄岳雄・梅本詩織・神山いづみ・堂野主税・中谷和彦
  • Organizer: 日本化学会第９３春季年会
  • Place of Presentation: 立命館大学（滋賀県）
• [Presentation] High-throughput Screening of Chemical Libraries for the Discovery of RNA-binding Compounds (2012)
  • Author(s): Asako Murata, Yasue Harada, Takeo Fukuzumi, Shiori Umemoto, Seongwang Im, Masaki Hagihara, Kazuhiko Nakatani
  • Organizer: RNA 2012, the 17th Annual Meeting of the RNA Society
  • Place of Presentation: University of Michigan (Ann Arbor, Michigan, USA)
• [Presentation] 大規模化合物ライブラリーのスクリーニングによる，RNA結合性化合物の探索 (2012)
  • Author(s): 村田亜沙子, 原田恭枝, 福澄岳雄, 梅本詩織, 任仙光, 萩原正規, 中谷和彦
  • Organizer: 日本化学会第92回春季年会
  • Place of Presentation: 慶応義塾大学（神奈川県）
• [Presentation] High-throughput Screening of Chemical Libraries for the Discovery of RNA-binding Compounds (2011)
  • Author(s): Asako Murata, Yasue Harada, Takeo Fukuzumi, Shiori Umemoto, Seongwang Im, Masaki Hagihara and Kazuhiko Nakatani
  • Organizer: RNA 2011
  • Place of Presentation: 国際会議場（京都府）
• [Presentation] Fluorescent indicator displacement assay for the discovery of RNA-binding ligands (2011)
  • Author(s): Asako Murata, Yasue Harada, Takeo Fukuzumi, Shiori Umemoto, Seongwang Im, Masaki Hagihara and Kazuhiko Nakatani
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県）