The Purine riboswitch, also known as G-box, is a highly conserved RNA structure that is involved in the regulation of purine salvage and biosynthesis in Bacteria. Originally, the G-box motif was discovered in the untranslated leader regions of five purine metabolism operons in Bacillus subtilis that are regulated by a transcription termination mechanism in response to the presence of hypoxanthine and guanine [12923093]. A riboswitch that recognizes guanine and discriminates against other purine analogs was then discovered in the leader region of the B. subtilis xpt and purE genes [12787499]. Another member of the G-box regulon in B. more

subtilis, the ydhL (pbuE) gene encoding a purine efflux pump, was found to be activated in response to high levels of adenine by an adenine-responsive riboswitch [14718920]. Two other adenine-responsive riboswitches were characterized in Clostridium perfringens and Vibrio vulnificus, where they control add genes encoding adenine deaminase [14718920]. All identified adenine- and guainine-responsive riboswitches conform to a common conserved RNA motif. The purine-specific class of riboswitches is characterized by one of the smallest metabolite-binding RNA domain. The preference of the pbuE riboswitch to adenine (versus guanine) was attributed to a single nucleotide substitution in the junction between stems P1 and P3. As an interesting exception, one member of purine riboswitch family located in the leader region of ribonucleotide reductase operon in Mesoplasma florum is specific to deoxyguanosine [17911257]. The solved crystal structures of adenine-, and guanine-responsive riboswitches in complexes with nucleobases revealed that recognition specificity is associated with Watson-Crick pairing of the encapsulated adenine and guanine ligands with uridine and cytosine, respectively [15610857]. Structure of the guanine-responsive riboswitch of the xpt gene in B. subtilis complexed with hypoxanthine was also determined [15549109]. Hypoxanthine functions to stabilize this structure and to promote the formation of a downstream transcriptional terminator element, thereby providing a mechanism for directly repressing gene expression in response to an increase in intracellular concentrations of metabolite. In conclusion, the purine riboswitches are structurally similar RNA motifs that control different purine metabolism genes in response to one or several purine nucleobases: adenine, guanine, and hypoxanthine.