Abstract：
The second messenger guanosine 3\',5\'-bis(diphosphate)/guanosine tetraphosphate (ppGpp) and guanosine 3\'-diphosphate 5\'-triphosphate/guanosine pentaphosphate (pppGpp) ((p)ppGpp) has been shown to be crucial for the survival of mycobacteria under hostile conditions. Unexpectedly, deletion of primary (p)ppGpp synthetase-Rel did not completely diminish (p)ppGpp levels leading to the discovery of novel bifunctional enzyme-RelZ, which displayed guanosine 5\'-monophosphate,3\'-diphosphate (pGpp), ppGpp, and pppGpp ((pp)pGpp) synthesis and RNAseHII activity. What conditions does it express itself under, and does it work in concert with Rel? The regulation of its transcription and whether the Rel enzyme plays a role in such regulation remain unclear. In this article, we have studied relZ promoter and compared its activity with rel promoter in different growth conditions. We observed that the promoter activity of relZ was constitutive; it is weaker than rel promoter, lies within 200 bp upstream of translation-start site, and it increased under carbon starvation. Furthermore, the promoter activity of relZ was compromised in the rel-knockout strain in the stationary phase. Our study unveils the dynamic regulation of relZ promoter activity by SigA and SigB sigma factors in different growth phases in mycobacteria. Importantly, elucidating the regulatory network of RelZ would enable the development of the targeted interventions for treating mycobacterial infections.
摘要：
第二信使鸟苷3'，已证明5'-二(二磷酸)/四磷酸鸟苷(ppGpp)和3'-二磷酸鸟苷5'-三磷酸鸟苷/五磷酸鸟苷(pppGpp)(((p)ppGpp))对于分枝杆菌在恶劣条件下的存活至关重要。出乎意料的是,初级（p）ppGpp合成酶-Rel的缺失并没有完全减少（p）ppGpp水平，导致发现新的双功能酶-RelZ，显示鸟苷5'-单磷酸，3\'-二磷酸（pGpp），ppGpp,和pppGpp((pp)pGpp)合成和RNAseHII活性。它在什么条件下表达自己，它的转录调节以及Rel酶是否在这种调节中起作用尚不清楚。在这篇文章中,我们研究了relZ启动子，并比较了其在不同生长条件下与rel启动子的活性。我们观察到relZ的启动子活性是组成型的；它比rel启动子弱，位于翻译起始位点上游200bp内，它在碳饥饿下增加。此外，rel敲除菌株在静止期的启动子活性受损。我们的研究揭示了在分枝杆菌的不同生长阶段，SigA和SigBsigma因子对relZ启动子活性的动态调节。重要的是,阐明RelZ的监管网络将有助于开发治疗分枝杆菌感染的靶向干预措施.
