title: An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism.
abstract: Over 30 years ago, ZTP (5-aminoimidazole-4-carboxamide riboside 5'-triphosphate), a modified purine biosynthetic intermediate, was proposed to signal 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria. However, the mechanisms by which this putative alarmone or its precursor ZMP (5-aminoimidazole-4-carboxamide ribonucleotide, also known as AICAR) brings about any metabolic changes remain unexplained. Herein, we report the existence of a widespread riboswitch class that is most commonly associated with genes related to de novo purine biosynthesis and one-carbon metabolism. Biochemical data confirm that members of this riboswitch class selectively bind ZMP and ZTP with nanomolar affinity while strongly rejecting numerous natural analogs. Indeed, increases in the ZMP/ZTP pool, caused by folate stress in bacterial cells, trigger changes in the expression of a reporter gene fused to representative ZTP riboswitches in vivo. The wide distribution of this riboswitch class suggests that ZMP/ZTP signaling is important for species in numerous bacterial lineages.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520-8103, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Yale University, Box 208103, New Haven, CT 06520-8103, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Nelson
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520-8103, USA; Department of Molecular Biophysics and Biochemistry, Yale University, Box 208103, New Haven, CT 06520-8103, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. Electronic address: ronald.breaker@yale.edu.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
mesh_terms: D001483:Base Sequence; D046969:Clostridium acetobutylicum / Q000235:genetics; D017124:Conserved Sequence; D015964:Gene Expression Regulation, Bacterial; D055029:Inverted Repeat Sequences; D008969:Molecular Sequence Data; D011687:Purines / Q000096:biosynthesis*; D012329:RNA, Bacterial / Q000235:genetics*; D058928:Riboswitch
chemical_list: D011687:Purines; D012329:RNA, Bacterial; D058928:Riboswitch