De novo purine biosynthesis in bacteria relies on an adequate supply of the tetrahydrofolate (THF) derivative 10f-THF. The purine biosynthetic intermediate ZTP (5-aminoimidazole-4-carboxamide riboside 5′-triphosphate) has been proposed to function as a sensor of 10f-THF deficiency, but the mechanism involved is unclear. A new study now shows that a widespread class of riboswitches bind to ZTP and its precursor ZMP (5-aminoimidazole-4-carboxamide ribonucleotide) with nanomolar affinity. Kim et al. show that the binding of the Z-nucleotides to these riboswitches — which are associated with genes involved in purine biosynthesis and central carbon metabolism — triggers the expression of downstream genes to maintain the cellular pool of 10f-THF. Biochemical data indicate that ZTP and ZMP accumulate and are sensed by the riboswitches when 10f-THF is deficient, which activates a gene expression programme to restore the levels of 10f-THF.
References
Kim, P. B. et al. An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism. Mol. Cell 57, 317–328 (2015)
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Kåhrström, C. Riboswitch control is key to ZTP mystery. Nat Rev Microbiol 13, 127 (2015). https://doi.org/10.1038/nrmicro3441
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DOI: https://doi.org/10.1038/nrmicro3441