An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism.
An ancient riboswitch class in bacteria regulates purine biosynthesis and one-carbon metabolism.
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DOI：
10.1016/j.molcel.2015.01.001
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发表时间：
2015-01-22
期刊：
影响因子：
16
通讯作者：
Breaker RR
中科院分区：
文献类型：
--
作者：
Kim PB;Nelson JW;Breaker RR
三十多年前，ZTP（5-氨基-4-咪唑甲酰胺核苷5 '-三磷酸），一种修饰的嘌呤生物合成中间体，被提出用于指示细菌中10-甲酰基-四氢叶酸（10 f-THF）缺乏。然而，这种假定的alarmone或其前体ZMP（5-氨基咪唑-4-甲酰胺核糖核苷酸，也称为AICAR）引起任何代谢变化的机制仍然无法解释。在这里，我们报告存在一个广泛的核糖开关类，这是最常见的与从头嘌呤生物合成和一碳代谢相关的基因。生物化学数据证实，这种核糖开关类的成员选择性结合ZMP和ZTP与纳摩尔亲和力，同时强烈拒绝许多天然类似物。事实上，在ZMP/ZTP池中的增加，引起的细菌细胞中的叶酸应激，触发的报告基因融合到代表性的ZTP核糖开关在体内的表达的变化。这种核糖开关类的广泛分布表明ZMP/ZTP信号传导对于许多细菌谱系中的物种是重要的。
Over thirty years ago, ZTP (5-amino-4-imidazole 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 confirms 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.