当前位置: X-MOL 学术Nat. Chem. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
An excited state underlies gene regulation of a transcriptional riboswitch
Nature Chemical Biology ( IF 14.8 ) Pub Date : 2017-07-17 00:00:00 , DOI: 10.1038/nchembio.2427
Bo Zhao , Sharon L Guffy , Benfeard Williams , Qi Zhang

Riboswitches control gene expression through ligand-dependent structural rearrangements of the sensing aptamer domain. However, we found that the Bacillus cereus fluoride riboswitch aptamer adopts identical tertiary structures in solution with and without ligand. Using chemical-exchange saturation transfer (CEST) NMR spectroscopy, we revealed that the structured ligand-free aptamer transiently accesses a low-populated (~1%) and short-lived (~3 ms) excited conformational state that unravels a conserved 'linchpin' base pair to signal transcription termination. Upon fluoride binding, this highly localized, fleeting process is allosterically suppressed, which activates transcription. We demonstrated that this mechanism confers effective fluoride-dependent gene activation over a wide range of transcription rates, which is essential for robust toxicity responses across diverse cellular conditions. These results unveil a novel switching mechanism that employs ligand-dependent suppression of an aptamer excited state to coordinate regulatory conformational transitions rather than adopting distinct aptamer ground-state tertiary architectures, exemplifying a new mode of ligand-dependent RNA regulation.

中文翻译:

兴奋状态是转录核糖开关基因调控的基础

核糖开关通过传感适体结构域的配体依赖性结构重排控制基因表达。但是,我们发现蜡状芽孢杆菌氟化物核糖开关适体在有或没有配体的溶液中采用相同的三级结构。使用化学交换饱和转移(CEST)NMR光谱,我们发现无结构的无配体适体瞬时进入低密度(〜1%)和短寿命(〜3 ms)的激发构象状态,从而破坏了保守的'linchpin'碱基对信号转录终止。氟化物结合后,这种高度局部化的短暂过程被变构抑制,从而激活了转录。我们证明了这种机制赋予了广泛的转录速率有效的氟化物依赖性基因激活,这对于在各种细胞条件下产生强大的毒性反应是必不可少的。
更新日期:2017-08-19
down
wechat
bug