THF-II riboswitch

The THF-II riboswitch is a conserved non-coding RNA structure found typically in the 5’ untranslated regions of bacterial mRNAs, where it regulates gene expression in response to binding tetrahydrofolic acid (THF) and closely related metabolites[1][3][4][5][6]. It adopts a simple, rod-like secondary and tertiary structure, with aptamer and expression platform regions largely overlapping, and recognizes THF via highly specific nucleotide-ligand contacts[1][3]. Ligand binding stabilizes specific local RNA conformations (notably in loop regions), promoting the formation of an anti-ribosome binding site (anti-RBS) stem that inhibits ribosome access, thereby shutting off translation[1][3][4]. While THF-II riboswitches have been proposed as potential novel antibiotic targets due to their bacterial specificity and essential regulatory role for folate-related metabolism, no drugs are currently approved to target them directly[4]. The THF-II riboswitch is distinct from the structurally related THF-I riboswitch, notably in its simpler architecture and more restricted ligand specificity[3][1].

Other names

Tetrahydrofolate-II riboswitchfolE RNA motif

Ligand binding (tetrahydrofolate or close analogs) induces a conformational switch that represses translation by preventing ribosome binding to the mRNA.