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RelA-SpoT Homolog toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis.
- Source :
-
Molecular cell [Mol Cell] 2021 Aug 05; Vol. 81 (15), pp. 3160-3170.e9. Date of Electronic Publication: 2021 Jun 25. - Publication Year :
- 2021
-
Abstract
- RelA-SpoT Homolog (RSH) enzymes control bacterial physiology through synthesis and degradation of the nucleotide alarmone (p)ppGpp. We recently discovered multiple families of small alarmone synthetase (SAS) RSH acting as toxins of toxin-antitoxin (TA) modules, with the FaRel subfamily of toxSAS abrogating bacterial growth by producing an analog of (p)ppGpp, (pp)pApp. Here we probe the mechanism of growth arrest used by four experimentally unexplored subfamilies of toxSAS: FaRel2, PhRel, PhRel2, and CapRel. Surprisingly, all these toxins specifically inhibit protein synthesis. To do so, they transfer a pyrophosphate moiety from ATP to the tRNA 3' CCA. The modification inhibits both tRNA aminoacylation and the sensing of cellular amino acid starvation by the ribosome-associated RSH RelA. Conversely, we show that some small alarmone hydrolase (SAH) RSH enzymes can reverse the pyrophosphorylation of tRNA to counter the growth inhibition by toxSAS. Collectively, we establish RSHs as RNA-modifying enzymes.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Bacterial Toxins genetics
Bacterial Toxins pharmacology
Gram-Positive Asporogenous Rods chemistry
Gram-Positive Asporogenous Rods metabolism
Guanosine Pentaphosphate chemistry
Ligases chemistry
Ligases genetics
Phosphorylation drug effects
Protein Biosynthesis drug effects
Protein Biosynthesis physiology
Protein Synthesis Inhibitors pharmacology
Pyrophosphatases
Ribosomes metabolism
Bacterial Toxins metabolism
Guanosine Pentaphosphate metabolism
Ligases metabolism
RNA, Transfer metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 81
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 34174184
- Full Text :
- https://doi.org/10.1016/j.molcel.2021.06.005