The SAH riboswitch was originally identified by bioinformatics as a conserved RNA-like structure located upstream of the methionine metabolism genes in various Proteobacteria and in some Actinobacteria [17621584]. Later, the SAM-IV riboswitch was shown to bind directly to S-adenosylhomocysteine (SAH) [18374645]. S-adenosylmethionine (SAM) is a common co-substrate involved in methyl group transfers and is synthesized from the methionine amino acid by the SAM synthase MetK. SAH is produced upon SAM-dependent methylation, and the intracellular balance of the two species has to be closely monitored to maintain cellular homeostasis and avoid toxicity [6760211]. more

The SAH riboswitch is important for maintaining the SAM/SAH ratio, as it up-regulates many of the genes involved in recycling of SAH to create more SAM. The up-regulation of downstream genes can be achieved through anti-terminator formation or exposure of SD sequence [18374645]. The ability of SAH riboswitch to differentiate SAH from SAM is especially remarkable given the larger cellular pool of SAM under normal conditions [6760211]. The x-ray crystal structure of the SAH riboswitch complexed with SAH was solved [20864509]. This structure reveals an unusual pseudoknot topology that creates a shallow groove on the surface of the RNA that binds SAH primarily through interactions with the adenine ring and methionine main chain atoms and discriminates against SAM through a steric mechanism.