Modulation of pre-miRNA processing by a small-molecule

• Project/Area Number: 25750393
• 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): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マイクロRNA / 小分子化合物 / 核酸 / 発現制御 / バイオテクロノジー / バイオテクノロジー

Outline of Final Research Achievements

This study　aimed to modulate the cleavage of pre-miRNAs (miRNA precursors) by a small-molecule compound. Small-molecule compounds that bind to a specific sequence in the pre-miRNA have been used to alter the cleavage reaction with Dicer, and thereby increase/decrease the production of the miRNA. Terminal loop sequences of pre-miRNA that bind to our newly designed naphthyridine derivative RND were obtained by in vitro selection from a pre-miR-29a mutant library with the randomized terminal loop region. Binding of RND to the obtained terminal sequences significantly interfere with the cleavage of the terminal loop mutants of pre-miR-29a. Gel shift analysis suggested that the inhibitory effect of RND might be caused by the formation of loop-loop complex between two terminal loop mutants upon binding of RND to the terminal loop.

Research Products

• [Journal Article] Exploratory Study on the RNA-Binding Structural Motifs by Library Screening Targeting pre-miRNA-29a. (2015)
  • Author(s): Fukuzumi, T.; Murata, A.; Aikawa, H.; Harada, Y.: Nakatani, K.
  • Journal Title: Chem. Eur. J. Volume: 21 Issue: 47 Pages: 16859-16867
  • DOI: 10.1002/chem.201502913
  • Peer Reviewed
• [Journal Article] Synthesis of 8-substituted adenine and adenosine libraries and the binding to pre-miR-29a (2014)
  • Author(s): Fukuzumi, T.; Aikawa, H.; Harada, Y.; Sugai, A.; Murata, A.; Nakatani, K.
  • Journal Title: Bull. Chem. Soc. Jpn. Volume: 87 Issue: 9 Pages: 1013-1015
  • DOI: 10.1246/bcsj.20140137
  • NAID: 130004687252
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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
• [Presentation] SPR-based in vitro selection of pre-miRNA loop mutant molecules that bind to the restrained naphthyridine dimer (2015)
  • Author(s): Yuki Mori, Yue Di, Ayako Sugai, Asako Murata, Kazuhiko Nakatani
  • Organizer: Pacifichem2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] A small-molecule inhibitor of pre-miR-29 maturation (2015)
  • Author(s): Asako Murata, Takahiro Otabe, Jinhua Zhang, Kazuhiko Nakatani
  • Organizer: Pacifichem2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Small molecule-Loop Interaction that interferes the maturation on process of pre-miRNA by Dicer (2015)
  • Author(s): Yuki Mori, Yue Di, Ayako Sugai, Asako Murata, Kazuhiko Nakatani
  • Organizer: ISNAC2015
  • Place of Presentation: 姫路
  • Year and Date: 2015-09-23
  • Int'l Joint Research
• [Presentation] In vitro selection of pre-miRNA loop mutant molecules that bind to the restrained naphthyridine dimer (2015)
  • Author(s): Asako Murata, Yuki Mori, Yue Di, Ayako Sugai, Kazuhiko Nakatani
  • Organizer: RNA2015, The 20th Annual Meeting of the RNA Society
  • Place of Presentation: Wisconsin, USA
  • Year and Date: 2015-05-26
  • Int'l Joint Research
• [Presentation] SPRを用いたin vitro selectionによるRND(the restrained naphthyridine dimer)結合性RNAアプタマーの探索 (2015)
  • Author(s): 森友紀、邸つき、須貝亜矢子、李金星、小田部尭広、相川春夫、村田亜沙子、中谷和彦
  • Organizer: 日本化学会第９５春季年会
  • Place of Presentation: 日本大学（千葉県、船橋）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] RNA結合性小分子の創成を指向したエンタルピー駆動型分子の設計と合成 (2015)
  • Author(s): 夏原望、邸つき、Mukherjee Sanjukta、村田亜沙子、中谷和彦
  • Organizer: 日本化学会第９５春季年会
  • Place of Presentation: 日本大学（千葉県、船橋）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] BzDANPによるRNAプロセシング阻害の速度論的解析 (2015)
  • Author(s): 小田部尭広、村田亜沙子、中谷和彦
  • Organizer: 日本化学会第９５春季年会
  • Place of Presentation: 日本大学（千葉県、船橋）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Suppression of miR-29a maturation by synthetic ligand (2014)
  • Author(s): Takahiro Otabe, Jinxin Li, Asako Murata, Kazuhiko Nakatani
  • Organizer: ISNAC2014
  • Place of Presentation: 北九州国際会議場（福岡県、小倉）
  • Year and Date: 2014-11-05 – 2014-11-07
• [Presentation] In vitro selection of pre-miR-29a loop mutant library against the restrained naphthyridine dimer (2014)
  • Author(s): Yuki Mori, Yue Di, Ayako Sugai, Takahiro Otabe, Jinxin Li, Haruo Aikawa, Asako Murata, Kazuhiko Nakatani
  • Organizer: ISNAC2014
  • Place of Presentation: 北九州国際会議場（福岡県、小倉
  • Year and Date: 2014-11-05 – 2014-11-07
• [Presentation] 小分子によるmiR-29a成熟過程の阻害 (2014)
  • Author(s): 小田部尭広、村田亜沙子、武井史恵、中谷和彦
  • Organizer: 日本ケミカルバイオロジー学会 第９回年会
  • Place of Presentation: 大阪大学（大阪府，豊中）
  • Year and Date: 2014-06-11 – 2014-06-13
• [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] 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）