Rational design of a synthetic mammalian riboswitch as a ligand-responsive -1 ribosomal frame-shifting stimulator

Lin, Ya-Hui; Chang, Kung-Yao

The two riboswitch-derived −1 PRF stimulators both possess ligand-induced base-triple interaction networks that surround the helical junctions of pseudoknot folds (14) (15) (16) (17) . However, it is challenging to design a specific liganddependent base-triple network within an RNA pseudoknot as well as to convert the ligand-responsive pseudoknot into a ligand-dependent −1 PRF stimulator. By contrast, the −1 PRF stimulators of coronaviruses belong to a family of wellcharacterized H-type pseudoknots (IBV-type pseudoknot) with a long stem 1 of at least 11 base pairs essential for stimulating −1 PRF efficiently (18) . Furthermore, in vitro selection methods capable of identifying RNA receptors for specific ligands of interest, and RNA aptamers for a variety of ligands are available (19) . Thus, the combination of a well-characterized −1 PRF stimulator and an aptamer of a specific ligand could provide a straightforward solution for rational design of a ligand-responsive −1 PRF stimulator.