The Institute of Scientific and Industrial Research, Osaka University


LAST UPDATE 2020/06/11

  • 研究者氏名
    Researcher Name

    村田亜沙子 Asako MURATA
    准教授 Associate Professor
  • 所属
    Professional Affiliation

    The Institute of Scientific and Industrial Research, Osaka University

    Department of Regulatory Bioorganic Chemistry
  • 研究キーワード
    Research Keywords

    non-coding RNA
    RNA structure
    Small molecule
Research Subject
Exploring of small-molecule ligands that regulate RNA structures and functions

研究の背景 Background

タンパク質に翻訳されないノンコーディングRNA(non-coding RNA: ncRNA)が注目されています。ncRNAは,発生や分化,がんを含む種々の生命現象に関わっており,次世代の創薬標的としても期待されています。しかし,RNAを標的とする低分子化合物の分子設計は難しいと考えられています。これは, 低分子化合物がRNAに結合する具体例が少なく,RNA-低分子化合物の相互作用に関する情報が不足していることが理由のひとつです。

Non-coding RNAs (ncRNA) are involved in various biological processes including development, cell differentiation, and cancer development. ncRNA is now considered as an attractive target for drug development, however, it remains a challenge to rationally design small molecules that bind to a specific RNA target because of the lack of information about the interaction between RNA and small molecules.

研究の目標 Outcome

RNA-低分子化合物の相互作用情報を得るためには, RNAに結合する化合物の例を増やし,それらの結合様式を詳細に調べることが必要です。そこで,化合物スクリーニングおよびセレクション法という2つのアプローチで,RNA-小分子のペアの探索研究を行っています。また,低分子化合物によってncRNAの構造を変化させることで,ncRNAの機能を調節する手法の開発も行っています。

Analyzing many examples of small molecule-RNA complex will provide clues for better understanding of the interaction between RNAs and small molecules. We are now exploring such small molecule–RNA pairs by high-throughput screening and in vitro selection methodology. In addition, we have been developing methods that utilize small molecules to modulate RNA structures and functions.

研究図Research Figure

Fig.1. High-throughput screening (HTS) of a large chemical library for molecules that bind to specific pre-miRNA using the fluorescent indicator displacement assay  

Fig.2. In vitro selection of RNA molecules that bind to a specific small molecule.

Fig.3. Activation of -1 ribosomal frame-shifting by stabilization of the pseudoknot structure with small-molecule binding.

文献 / Publications

Nat. Genet. 2020, 52, 146-159.; Nucl. Acids Res. 2019, 47, 10906-10913.; Methods 2019, 167, 78-91.; Bioorg. Med. Chem. 2019, 27, 2140-2148; Chem. Eur. J. 2018, 24, 18115-18122.; Nucleic Acids Res. 2018, 46, 8079-8089.