Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.
Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.
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DOI：
10.1073/pnas.1720406115
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发表时间：
2018-06-05
影响因子：
11.1
通讯作者：
Breaker RR
中科院分区：
文献类型：
--
作者：
Sherlock ME;Sudarsan N;Breaker RR
细菌和其他生物体广泛使用源自核糖核苷酸或其衍生物的信号分子。以前，已经发现了五种核糖开关类型，它们可以检测四种RNA衍生的信号分子：c-di-GMP，c-di-AMP，c-AMP-GMP和ZTP。我们现在报告的发现和生物化学验证细菌核糖开关的广泛alarmone鸟苷四磷酸（ppGPP），这标志着代谢和生理适应饥饿。这些发现扩大了核糖开关和核糖核苷酸样信号分子之间的天然伙伴关系的数量，并提供了用于检测细胞中ppGpp产生的基于RNA的传感器。核糖开关是某些mRNA的非编码部分，其结合代谢物、辅酶、信号分子或无机离子配体并调节基因表达。大多数已知的核糖开关感测RNA单体的衍生物。配体化学组成的这种偏差与广泛存在的核糖开关类首先出现在RNA世界的假设是一致的，这被认为是在蛋白质存在之前就存在的。在这里，我们报告的发现和生物化学验证的天然核糖开关类，选择性地结合鸟苷四磷酸（ppGPP），广泛的信号分子和细菌的“alarmone”来自核糖核苷酸GTP。预测ppGpp的核糖开关调节参与支链氨基酸生物合成和运输的基因，以及以前没有被牵连到其信号网络的一部分的其他基因类别。这种新发现的核糖开关-alarmone伙伴关系支持了一种假设，即现代细胞保留了突出的RNA世界信号通路来控制关键的生物过程。
Bacteria and other organisms make extensive use of signaling molecules that are derived from ribonucleotides or their derivatives. Previously, five riboswitch classes had been discovered that sense the four RNA-derived signaling molecules: c-di-GMP, c-di-AMP, c-AMP-GMP, and ZTP. We now report the discovery and biochemical validation of bacterial riboswitches for the widespread alarmone guanosine tetraphosphate (ppGpp), which signals metabolic and physiological adaptations to starvation. These findings expand the number of natural partnerships between riboswitches and ribonucleotide-like signaling molecules, and provide RNA-based sensors for detecting ppGpp production in cells. Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch classes first emerged during the RNA World, which is proposed to have existed before proteins were present. Here we report the discovery and biochemical validation of a natural riboswitch class that selectively binds guanosine tetraphosphate (ppGpp), a widespread signaling molecule and bacterial “alarmone” derived from the ribonucleotide GTP. Riboswitches for ppGpp are predicted to regulate genes involved in branched-chain amino acid biosynthesis and transport, as well as other gene classes that previously had not been implicated to be part of its signaling network. This newfound riboswitch–alarmone partnership supports the hypothesis that prominent RNA World signaling pathways have been retained by modern cells to control key biological processes.
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DOI：
10.1093/bioinformatics/btt509
发表时间：
2013-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Kuipers, OP
DOI：
10.1073/pnas.1419264112
发表时间：
2015-04-28
影响因子：
11.1
作者：
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通讯作者：
Breaker, Ronald R.
影响因子：
4.5
作者：
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通讯作者：
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影响因子：
16
作者：
Kim PB;Nelson JW;Breaker RR
通讯作者：
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