The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES.
The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES.
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结核分枝杆菌sRNA F6修饰必需伴侣蛋白GroEL 2和GroES的表达。
DOI：
10.1128/spectrum.01095-21
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发表时间：
2021-10-31
影响因子：
3.7
通讯作者：
Arnvig KB
中科院分区：
文献类型：
--
作者：
Houghton J;Rodgers A;Rose G;D'Halluin A;Kipkorir T;Barker D;Waddell SJ;Arnvig KB
在确定结核分枝杆菌为结核病的病原近140年后，其生物学的重要方面仍然缺乏描述。对于基因表达和RNA生物学的转录后控制作用知之甚少，包括迄今为止鉴定的大多数小RNA （sRNAs）的作用。我们对结核分枝杆菌sRNA F6进行了详细的研究，发现它依赖于SigF的表达，并在体外饥饿条件下和小鼠感染模型中显著诱导。通过体外饥饿感染模型对F6的进一步研究表明，F6会影响必需伴侣蛋白GroEL2和GroES的表达。我们的研究结果指出F6在低代谢活动时期的作用，通常与人类肉芽肿中结核分枝杆菌的长期存活有关。在最成功的病原体之一结核分枝杆菌中，通过小调控rna （sRNAs）控制基因表达的了解甚少。在这里，我们对sRNA F6进行了深入的表征，包括其在不同感染模型中的表达以及sRNA缺失后观察到的差异基因表达。我们的研究结果表明，F6的缺失导致两种必需的伴侣蛋白GroEL2和GroES的失调，并且表明F6在结核分枝杆菌在人类宿主中的长期生存和持续中起作用。
Almost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of posttranscriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA F6 and shown it to be dependent on SigF for expression and significantly induced in starvation conditions in vitro and in a mouse model of infection. Further exploration of F6 using an in vitro starvation model of infection indicates that F6 affects the expression of the essential chaperonins GroEL2 and GroES. Our results point toward a role for F6 during periods of low metabolic activity typically associated with long-term survival of M. tuberculosis in human granulomas. IMPORTANCE Control of gene expression via small regulatory RNAs (sRNAs) is poorly understood in one of the most successful pathogens, Mycobacterium tuberculosis. Here, we present an in-depth characterization of the sRNA F6, including its expression in different infection models and the differential gene expression observed upon deletion of the sRNA. Our results demonstrate that deletion of F6 leads to dysregulation of the two essential chaperonins GroEL2 and GroES and, moreover, indicate a role for F6 in the long-term survival and persistence of M. tuberculosis in the human host.