An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism

Mol Cell. 2015 Jan 22;57(2):317-28. doi: 10.1016/j.molcel.2015.01.001.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Clostridium acetobutylicum / genetics
  • Conserved Sequence
  • Gene Expression Regulation, Bacterial
  • Inverted Repeat Sequences
  • Molecular Sequence Data
  • Purines / biosynthesis*
  • RNA, Bacterial / genetics*
  • Riboswitch*


  • Purines
  • RNA, Bacterial
  • Riboswitch