Ribonuclease toxin RelE1 inhibits growth of <i>Mycobacterium tuberculosis</i> through specific cleavage of the ribosomal anti-Shine–Dalgarno region

Toxin-antitoxin (TA) systems are central to bacterial immunity, genome maintenance, and pathogenicity. Toxins of TA systems use diverse strategies to control bacterial growth and represent attractive therapeutic targets to fight pathogens. In this work, we have investigated the toxic mechanism of the three RelE toxins of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. Structural studies showed that RelBE1, RelBE2, and RelBE3 TA complexes share conserved structural motifs distinct from the RelBE complex of Escherichia coli. Although RelE homologs have previously been reported to perform ribosome-dependent messenger RNA (mRNA) cleavage, detection of cleavage products by nEMOTE demonstrated that only RelE3 targets mRNA. In contrast, in vitro and in vivo analyses using Mycobacterium smegmatis and M. tuberculosis revealed that RelE1 is a site-specific RNase, able to cleave 16S rRNA from free 30S and formed 70S ribosomes, to release the anti-Shine-Dalgarno region and prevent translation. This stunning mode of action, which is likely shared with RelE2, demonstrates that there is broader diversity for toxic mechanisms within the widespread RelE family.

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Publication Details

Journal
Nucleic Acids Research
Published
2025-11-13
DOI
https://doi.org/10.1093/nar/gkaf1070
Primary Topic
Bacterial Genetics and Biotechnology
Type
article
Field-Weighted Citation Impact
0.00

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article

Ribonuclease toxin RelE1 inhibits growth of Mycobacterium tuberculosis through specific cleavage of the ribosomal anti-Shine–Dalgarno region

Xibing Xu, Laurent Falquet, Tom J Arrowsmith, Tim R. Blower et al.
Nucleic Acids Research
Bacterial Genetics and Biotechnology
article

Ribonuclease toxin RelE1 inhibits growth of Mycobacterium tuberculosis through specific cleavage of the ribosomal anti-Shine–Dalgarno region

Xibing Xu, Laurent Falquet, Tom J Arrowsmith, Tim R. Blower, Roland Barriot, Hatice Akarsu, Moïse Mansour, Izaak N. Beck, Pierre Genevaux, Peter Redder, Hussein Hamze, Xue Han, C. Pagès, Paul Chansigaud
article en

Abstract

Toxin-antitoxin (TA) systems are central to bacterial immunity, genome maintenance, and pathogenicity. Toxins of TA systems use diverse strategies to control bacterial growth and represent attractive therapeutic targets to fight pathogens. In this work, we have investigated the toxic mechanism of the three RelE toxins of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. Structural studies showed that RelBE1, RelBE2, and RelBE3 TA complexes share conserved structural motifs distinct from the RelBE complex of Escherichia coli. Although RelE homologs have previously been reported to perform ribosome-dependent messenger RNA (mRNA) cleavage, detection of cleavage products by nEMOTE demonstrated that only RelE3 targets mRNA. In contrast, in vitro and in vivo analyses using Mycobacterium smegmatis and M. tuberculosis revealed that RelE1 is a site-specific RNase, able to cleave 16S rRNA from free 30S and formed 70S ribosomes, to release the anti-Shine-Dalgarno region and prevent translation. This stunning mode of action, which is likely shared with RelE2, demonstrates that there is broader diversity for toxic mechanisms within the widespread RelE family.

Nucleic Acids ResearchVol. 53(21)
New England Biolabs (United States) (US), SIB Swiss Institute of Bioinformatics (CH), Centre National de la Recherche Scientifique (FR), University of Fribourg (CH), Durham University (GB), Centre de Biologie du Développement (FR), Laboratoire de Microbiologie et Génétique Moléculaires (FR)
National Science Foundation, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Natural Science Foundation of China, China Scholarship Council, Centre National de la Recherche Scientifique
Openalex Percentile: Top 63%
Bacterial Genetics and Biotechnology
DOIOpen Access PDFOpenAlex
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