The SAM-IV riboswitch was originally identified by bioinformatics as a conserved RNA-like structure located upstream of the sulfur metabolism genes in various Actinomycetales species [17621584]. Later, the SAM-IV riboswitch was shown to bind directly to S-adenosylmethionine (SAM) [18369181]. SAM is a common co-substrate involved in methyl group transfers and is synthesized from the methionine amino acid by the SAM synthase MetK. The SAM-IV-containing intergenic region upstream of the Streptomyces coelicolor gene SCO2146 was used for experimental validation of this genetic regulatory element. The SAM-IV aptamers are followed by predicted rho-independent transcription terminators, but many aptamers are near the predicted start of their downstream gene, suggesting the sequestration of the ribosome-binding site and inhibition translation of downstream genes. more

The SAM-IV riboswitches have similarities to the ligand-binding core of SAM-I riboswitches, but have numerous differences elsewhere in architecture and nucleotide identities. . The ligand binding sites are also similar although they differ in the scaffolding, and the evolutionary relationship of the two riboswitches is still unclear [18369181].