Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response

eLife

Michael Y Galperin¹  Xinfeng Li²  Fang Chen²  Xiaojian Cao²  Xiaoyu Liu²  Jinfeng Xiao²  Shan-Ho Chou²  Jin He²  Binda T Andongma²  Qing Tang² 

[1] National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, United States;State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China;

关键词: mycobacteria;    starvation response;    global regulator CarD;    Clp protease;    antisense RNA;    stress response;    Other;   

DOI  :  10.7554/eLife.73347

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY