Rational construction of eukaryotic riboswitches requiring less energy for their conformational changes

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05846
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Ehime University
• Principal Investigator: Ogawa Atsushi 愛媛大学, プロテオサイエンスセンター, 准教授 (30442940)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: リボスイッチ / 発現制御 / 合成生物学

Outline of Final Research Achievements

We rationally constructed three types of energy-saving, eukaryotic riboswitches (ligand-responsive regulatory RNAs) that function in eukaryotic translation systems. The first one upregulates translation mediated by a 3' cap-independent translation element (3' CITE) in response to its specific ligand. The second one ligand-dependently downregulates translation mediated by an internal ribosome entry site (IRES). The last one ligand-responsively downregulates canonical translation. Because all of them require no major hybridization switches for gene regulation, they require less energy for their conformational changes, thus showing higher switching efficiencies. In addition, their ligand-specificity can easily be changed just by replacing a part of them (specifically, the aptamer domain) to obtain a riboswitch responsive to a user-defined ligand.

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した省エネ型リボスイッチは、分子応答制御時に「鎖置換」を伴わないため、エネルギーロスが少なく、高い制御効率を発揮する。また、分子特異性の変更も容易であることから、任意の分子の濃度に応じて任意のタンパク質の生産量を広範囲にコントロールすることが可能となる。このような人工の分子応答性遺伝子発現制御システムは、合成生物学を含む幅広い学問領域において、基盤技術としての利用が期待される。