A protein-dependent riboswitch activates ribosomal frameshifting in cardioviruses

Published: 18 August 2026| Version 1 | DOI: 10.17632/78kj389b6v.1
Contributors:
, Chris Hill

Description

Raw data and analyses corresponding to figures and supplementary material in Betts et al, 2026 -- Abstract: Programmed -1 ribosomal frameshifting (PRF) is a translational control mechanism used by RNA viruses to regulate the relative abundance of proteins encoded in different reading frames. Cardioviruses exhibit the highest known PRF efficiency, with ~85% of ribosomes shifting into the -1 frame. This unusual event requires an interaction between the viral 2A protein and a stimulatory element in the RNA genome, but the basis for protein-dependence is unclear. To address this, here we investigate structure and dynamics of the PRF signal in Theiler's murine encephalitis virus (TMEV). By combining X-ray crystallography, small angle X-ray scattering (SAXS) and single-molecule fluorescence resonance energy transfer (smFRET), we show that 2A binding switches the RNA from a stem-loop conformation into a pseudoknot, and we demonstrate that pseudoknot formation is essential for efficient PRF in vitro and in cells. Together, these findings illustrate how the cardiovirus PRF element behaves as a protein-dependent riboswitch, defining the molecular mechanism by which frameshifting is conditionally activated.

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Biochemistry, Biophysics, Protein-RNA Interaction, RNA, Single Molecule Imaging, Picornavirus

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