A spermidine riboswitch class in bacteria exploits a close variant of an aptamer for the enzyme cofactor S-adenosylmethionine

Natural polyamines such as spermidine and spermine cations have characteristics that make them highly likely to be sensed by riboswitches, such as their general affinity to polyanionic RNA and their broad contributions to cell physiology. Despite previous claims that polyamine riboswitches exist, evidence of their biological functions has remained unconvincing. Here, we report that rare variants of bacterial S-adenosylmethionine-I (SAM-I) riboswitches reject SAM and have adapted to selectively sense spermidine. These spermidine-sensing riboswitch variants are associated with genes whose protein products are directly involved in the production of spermidine and other polyamines. Biochemical and genetic assays demonstrate that representatives of this riboswitch class robustly function as genetic “off” switches, wherein spermidine binding causes premature transcription termination to suppress the expression of polyamine biosynthetic genes. These findings confirm the existence of natural spermidine-sensing riboswitches in bacteria and expand the list of variant riboswitch classes that have adapted to bind different ligands. [Display omitted] •Natural spermidine-sensing riboswitches exist in bacteria•Rare SAM-I riboswitch variants have adapted to sense spermidine•Spermidine riboswitches repress polyamine biosynthesis genes Salvail et al. demonstrate that rare variants of bacterial S-adenosylmethionine-I (SAM-I) riboswitches reject SAM and selectively sense spermidine to repress the expression of polyamine biosynthesis genes. This unusual class of RNA genetic switches expands the list of variant riboswitches that have evolved altered ligand-binding specificity.