Regulation of the ThiM riboswitch is facilitated by the trapped structure formed during transcription of the wild-type sequence.

The ThiM riboswitch from Escherichia coli is a typical mRNA device that modulates downstream gene expression by sensing TPP. The helix-based RNA folding theory is used to investigate its detailed regulatory behaviors in cells. This RNA molecule is transcriptionally trapped in a state with the unstructured SD sequence in the absence of TPP, which induces downstream gene expression. As a key step to turn on gene expression, formation of this trapped state (the genetic ON state) highly depends on the co-transcriptional folding of its wild-type sequence. Instead of stabilities of the genetic ON and OFF states, the transcription rate, pause, and ligand levels are combined to affect the ThiM riboswitch-mediated gene regulation, which is consistent with a kinetic control model.