Eukaryotic artificial ON-riboswitches that respond efficiently to mid-sized short peptides.

Bioorg Med Chem Lett

Proteo-Science Center, Ehime University, 3 Bunkyo, Matsuyama, Ehime 790-8577, Japan. Electronic address:

Published: September 2022

AI Article Synopsis

  • The study developed eukaryotic ON-riboswitches using two types of Arg-rich peptides (Rev-pep and Tat-pep) as ligands, demonstrating effective regulation of gene expression.
  • The riboswitches exhibited significantly higher efficiency at low concentrations of ligands compared to smaller ligands, with strong specificity towards their respective peptides despite their sequence similarity.
  • This pair of riboswitches offers promising applications as gene regulators or biosensors due to their high responsiveness and versatility in various biological contexts.

Article Abstract

We chose two types of mid-sized Arg-rich peptides (Rev-pep and Tat-pep) as ligands and used their aptamers to construct efficient eukaryotic ON-riboswitches (ligand-dependently upregulating riboswitches). Due to the aptamers' high affinities, the best Rev-pep-responsive and Tat-pep-responsive riboswitches obtained showed much higher switching efficiencies at low ligand concentrations than small ligand-responsive ON-riboswitches in the same mechanism. In addition, despite the high sequence similarity of Rev-pep and Tat-pep, the two best riboswitches were almost insensitive to each other's peptide ligand. Considering the high responsiveness and specificity along with the versatility of the expression platform used and the applicability of Arg-rich peptides, this orthogonal pair of riboswitches would be widely useful eukaryotic gene regulators or biosensors.

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http://dx.doi.org/10.1016/j.bmcl.2022.128839DOI Listing

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