Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8103, USA.
Cell Rep. 2023 Dec 26;42(12):113571. doi: 10.1016/j.celrep.2023.113571. Epub 2023 Dec 12.
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.
天然多胺，如亚精胺和精胺阳离子，具有使其极有可能被核糖开关感知的特性，例如它们对聚阴离子 RNA 的普遍亲和力和对细胞生理学的广泛贡献。尽管先前有报道称多胺核糖开关存在，但它们的生物学功能的证据仍然不令人信服。在这里，我们报告说细菌 S-腺苷甲硫氨酸-I（SAM-I）核糖开关的罕见变体拒绝 SAM 并已适应选择性感知亚精胺。这些亚精胺感应核糖开关变体与编码其蛋白质产物直接参与亚精胺和其他多胺产生的基因相关。生化和遗传测定表明，该类核糖开关的代表作为遗传“关闭”开关，其中亚精胺结合导致转录提前终止以抑制多胺生物合成基因的表达。这些发现证实了细菌中天然亚精胺感应核糖开关的存在，并扩展了适应结合不同配体的变体核糖开关类别的列表。
