Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response.
Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response.
复制标题
Clp蛋白酶和反义RNA共同调节全局调节因子CarD介导分枝杆菌饥饿反应
作者：
Li X;Chen F;Liu X;Xiao J;Andongma BT;Tang Q;Cao X;Chou SH;Galperin MY;He J
在饥饿条件下，细菌倾向于通过减少rRNA合成来减缓其翻译速率，但它们实现的方式可能因细菌而异。在分枝杆菌属物种中，rRNA的转录由RNA聚合酶（RNAP）辅助转录因子CarD激活，其直接与RNAP相互作用以稳定在rRNA基因上形成的RNAP-启动子开放复合物。CardD的功能已被广泛研究，但控制其表达的机制仍不清楚。在这里，我们报告说，当分枝杆菌细胞从营养丰富切换到营养缺乏条件时，CardD的水平受到严格调控。在翻译水平上，cardD的反义RNA（AscarD）以SigF依赖的方式被诱导与cardD mRNA结合并抑制其翻译，而在翻译后水平上，胞内残留的CarD被Clp蛋白酶迅速降解。因此，AscarD与Clp蛋白酶协同作用，降低CardD水平，以帮助分枝杆菌细胞科普营养应激。总之，我们的工作阐明了CardD的调节模式，并描绘了一个新的机制，分枝杆菌饥饿反应，这是重要的适应和持久性的分枝杆菌病原体在宿主环境中。
Under starvation conditions, bacteria tend to slow down their translation rate by reducing rRNA synthesis, but the way they accomplish that may vary in different bacteria. In Mycobacterium species, transcription of rRNA is activated by the RNA polymerase (RNAP) accessory transcription factor CarD, which interacts directly with RNAP to stabilize the RNAP-promoter open complex formed on rRNA genes. The functions of CarD have been extensively studied, but the mechanisms that control its expression remain obscure. Here, we report that the level of CarD was tightly regulated when mycobacterial cells switched from nutrient-rich to nutrient-deprived conditions. At the translational level, an antisense RNA of carD (AscarD) was induced in a SigF-dependent manner to bind with carD mRNA and inhibit CarD translation, while at the post-translational level, the residual intracellular CarD was quickly degraded by the Clp protease. AscarD thus worked synergistically with Clp protease to decrease the CarD level to help mycobacterial cells cope with the nutritional stress. Altogether, our work elucidates the regulation mode of CarD and delineates a new mechanism for the mycobacterial starvation response, which is important for the adaptation and persistence of mycobacterial pathogens in the host environment.
影响因子：
4.1
作者：
Schultz D;Schlüter R;Gerth U;Lalk M
通讯作者：
Lalk M