Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response
- Huazhong Agricultural University, China
- National Institutes of Health, United States
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1, 4, 5 and 6. These Source Data contain the numerical data used to generate the figures.
Article and author information
Author details
Michael Y Galperin
Funding
National Natural Science Foundation of China (31770087)
- Jin He
National Natural Science Foundation of China (31900057)
- Qing Tang
National Natural Science Foundation of China (31970074)
- Jin He
National Natural Science Foundation of China (32171424)
- Jin He
China Postdoctoral Science Foundation (2019M662654)
- Xinfeng Li
Intramural Research Program of the U.S. National Library of Medicine at the NIH
- Michael Y Galperin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Publication history
- Preprint posted: April 15, 2021 (view preprint)
- Received: August 25, 2021
- Accepted: January 25, 2022
- Accepted Manuscript published: January 26, 2022 (version 1)
- Version of Record published: February 7, 2022 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response
eLife 11:e73347.
https://doi.org/10.7554/eLife.73347
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