Yousuf Suhail, Angara Rajendra, Vindal Vaibhav, Ranjan Akash
Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India.
Computational and Functional Genomics Group, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana 500001, India Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Gachibowli, Telangana 500046, India.
Microbiology (Reading). 2015 Mar;161(Pt 3):463-76. doi: 10.1099/mic.0.000017. Epub 2014 Dec 19.
Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis. Lipids are assumed to be the major source of energy during dormancy. Here, we report the characterization of a starvation-inducible, lipid-responsive transcriptional regulator, Rv0494, divergently transcribed from the Rv0493c probable operon. The striking difference in the transcriptional regulatory apparatus between mycobacteria and other well-studied organisms, such as Escherichia coli, is the organization of mycobacterial promoters. Mycobacterial promoters have diverse architectures and most of these promoters function inefficiently in E. coli. In this study, we characterized the promoter elements of Rv0494 along with the sigma factors required for transcription initiation. Rv0494 promoter activity increased under nutrient starvation conditions and was transcribed via two promoters: the promoter proximal to the translational start site was active under standard growth conditions, whilst both promoters contributed to the increased activity seen during starvation, with the major contribution from the distal promoter. Furthermore, Rv0494 translation initiated at a codon located 9 bp downstream of the annotated start codon. Rv0494 bound to its upstream sequence to auto-regulate its own expression; this binding was responsive to long-chain fatty acyl-CoA molecules. We further report Rv0494-mediated transcriptional regulation of the Rv2326c gene - a probable transmembrane ATP-binding transporter encoding gene.
脂肪酸代谢在结核分枝杆菌的存活和发病机制中起着重要作用。脂质被认为是休眠期间的主要能量来源。在此，我们报道了一种饥饿诱导型、脂质响应转录调节因子Rv0494的特性，它与Rv0493c可能的操纵子反向转录。分枝杆菌与其他经过充分研究的生物体（如大肠杆菌）之间转录调控机制的显著差异在于分枝杆菌启动子的组织形式。分枝杆菌启动子具有多样的结构，并且这些启动子中的大多数在大肠杆菌中功能低效。在本研究中，我们对Rv0494的启动子元件以及转录起始所需的sigma因子进行了特性分析。Rv0494启动子活性在营养饥饿条件下增加，并且通过两个启动子进行转录：靠近翻译起始位点的启动子在标准生长条件下具有活性，而在饥饿期间观察到的活性增加是由两个启动子共同作用的结果，其中主要贡献来自远端启动子。此外，Rv0494的翻译起始于注释起始密码子下游9 bp处的一个密码子。Rv0494与其上游序列结合以自动调节自身表达；这种结合对长链脂肪酰辅酶A分子有响应。我们进一步报道了Rv介导的Rv2326c基因的转录调控，Rv2326c是一个可能编码跨膜ATP结合转运蛋白的基因。
