Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes.
Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes.
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DOI：
10.1111/j.1365-2958.2012.08115.x
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发表时间：
2012-07
影响因子：
3.6
通讯作者：
Roe JH
中科院分区：
文献类型：
--
作者：
Kim MS;Dufour YS;Yoo JS;Cho YB;Park JH;Nam GB;Kim HM;Lee KL;Donohue TJ;Roe JH
许多硫醇活性化合物引起氧化应激，其中细胞通过激活由硫醇传感器调节的生存策略来抵消。在天蓝色链霉菌中，一对sigma/antisigma对SigR/RsrA控制着对硫醇氧化应激的反应。为了揭示其完整的生理功能，采用染色质免疫沉淀结合序列和转录分析的方法，鉴定了天蓝色链霉菌中108个SigR靶基因，并预测了放线菌之间的同源调控子。除了已报道的与硫醇稳态、蛋白质降解和核糖体调节相关的基因外，还发现了额外的操纵子，表明这个全球调控因子具有新的功能。我们证明，在硫醇氧化应激期间，SIGR维持看家西格玛因子HRDB的水平和活性，这是一种新的应激反应策略。我们还发现，SigR保护细胞免受紫外线和硫醇反应损伤，修复UvrA参与其中。使用改进的SIGR结合序列模型，预测了42株放线菌中的SIGR同源物及其靶标。这揭示了一组保守的核心SIGR靶点，功能包括硫醇动态平衡、蛋白质质量控制、可能的转录和翻译调控、黄素介导的氧化还原反应和铁-S传递。SigR调节子的组成揭示了一种强大的保守的生理机制来处理从细菌到人类的硫醇氧化应激。
Numerous thiol-reactive compounds cause oxidative stress where cells counteract by activation of survival strategies regulated by thiol-based sensors. In Streptomyces coelicolor, a model actinomycete, a sigma/antisigma pair SigR/RsrA controls the response to thiol-oxidative stress. To unravel its full physiological functions, chromatin immuno-precipitation combined with sequence and transcript analyses were employed to identify 108 SigR target genes in S. coelicolor and to predict orthologous regulons across actinomycetes. In addition to reported genes for thiol homeostasis, protein degradation and ribosome modulation, 64 additional operons were identified suggesting new functions of this global regulator. We demonstrate that SigR maintains the level and activity of the housekeeping sigma factor HrdB during thiol-oxidative stress, a novel strategy for stress responses. We also found that SigR defends cells against UV and thiol-reactive damages, in which repair UvrA takes a part. Using a refined SigR-binding sequence model, SigR orthologues and their targets were predicted in 42 actinomycetes. This revealed a conserved core set of SigR targets to function for thiol homeostasis, protein quality control, possible modulation of transcription and translation, flavin-mediated redox reactions, and Fe-S delivery. The composition of the SigR regulon reveals a robust conserved physiological mechanism to deal with thiol-oxidative stress from bacteria to human.