| Structural highlights
Function
RELE_MYCTU Toxic component of a type II toxin-antitoxin (TA) system. Has RNase activity (By similarity). Overexpression in M.tuberculosis or M.smegmatis inhibits colony formation in a bacteriostatic rather than bacteriocidal fashion. Its toxic effect is neutralized by coexpression with cognate antitoxin RelB (shown only for M.smegmatis).[1] [2] [3] [4] In combination with RelB represses its own promoter. Has been seen to bind DNA in complex with cognate antitoxin RelB but not alone.
Publication Abstract from PubMed
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.
Ribonuclease toxin RelE1 inhibits growth of Mycobacterium tuberculosis through specific cleavage of the ribosomal anti-Shine-Dalgarno region.,Han X, Beck IN, Mansour M, Arrowsmith TJ, Barriot R, Chansigaud P, Pages C, Hamze H, Akarsu H, Falquet L, Redder P, Xu X, Blower TR, Genevaux P Nucleic Acids Res. 2025 Nov 13;53(21):gkaf1070. doi: 10.1093/nar/gkaf1070. PMID:41242526[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Korch SB, Contreras H, Clark-Curtiss JE. Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages. J Bacteriol. 2009 Mar;191(5):1618-30. doi: 10.1128/JB.01318-08. Epub 2008 Dec 29. PMID:19114484 doi:http://dx.doi.org/10.1128/JB.01318-08
- ↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
- ↑ . PMID:20061486
- ↑ Yang M, Gao C, Wang Y, Zhang H, He ZG. Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS One. 2010 May 17;5(5):e10672. doi: 10.1371/journal.pone.0010672. PMID:20498855 doi:http://dx.doi.org/10.1371/journal.pone.0010672
- ↑ Han X, Beck IN, Mansour M, Arrowsmith TJ, Barriot R, Chansigaud P, Pagès C, Hamze H, Akarsu H, Falquet L, Redder P, Xu X, Blower TR, Genevaux P. Ribonuclease toxin RelE1 inhibits growth of Mycobacterium tuberculosis through specific cleavage of the ribosomal anti-Shine-Dalgarno region. Nucleic Acids Res. 2025 Nov 13;53(21):gkaf1070. PMID:41242526 doi:10.1093/nar/gkaf1070
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