D'Halluin, Alexandre;
Kipkorir, Terry;
Hubert, Catherine;
Barker, Declan;
Arnvig, Kristine B;
(2025)
A Mycobacterium tuberculosis Mbox controls a conserved, small upstream ORF via a translational expression platform and rho-dependent termination of transcription.
RNA
, Article rna.080735.125. 10.1261/rna.080735.125.
(In press).
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Abstract
Magnesium is vital for bacterial survival, and its homeostasis is tightly regulated. Intracellular pathogens like Mycobacterium tuberculosis (Mtb) often face host-mediated magnesium limitation, which can be counteracted by upregulating the expression of Mg²⁺ transporters. This upregulation may be via Mg²⁺-sensing regulatory RNA such as the Bacillus subtilis ykoK Mbox riboswitch, which acts as a transcriptional “OFF-switch” under high Mg²⁺ conditions. Mtb encodes two Mbox elements with strong similarity to the ykoK Mbox. In the current study, we characterize the Mbox encoded upstream of the Mtb pe20 operon, which is required for growth in low Mg²⁺/low pH. We show that this switch operates via a translational expression platform and Rho-dependent transcription termination, which is the first such case reported for an Mbox. Moreover, we show that the switch directly controls a small ORF encoded upstream of pe20. We have annotated this highly conserved uORF rv1805A, but its role remains unclear. Interestingly, a homologous gene exists outside the Mbox-regulated context, suggesting functional importance beyond magnesium stress. Overall, this study uncovers a dual mechanism of riboswitch-regulation in Mtb, combining translational control with Rho-mediated transcription termination. These findings expand our understanding of RNA-based gene regulation in mycobacteria, with implications for pathogenesis and stress adaptation.
| Type: | Article |
|---|---|
| Title: | A Mycobacterium tuberculosis Mbox controls a conserved, small upstream ORF via a translational expression platform and rho-dependent termination of transcription |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1261/rna.080735.125 |
| Publisher version: | https://doi.org/10.1261/rna.080735.125 |
| Language: | English |
| Additional information: | This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217954 |
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