RelA-SpoT Homolog toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00543583" target="_blank" >RIV/61388963:_____/21:00543583 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.molcel.2021.06.005" target="_blank" >https://doi.org/10.1016/j.molcel.2021.06.005</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.molcel.2021.06.005" target="_blank" >10.1016/j.molcel.2021.06.005</a>
Alternative languages
Result language
angličtina
Original language name
RelA-SpoT Homolog toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
<a href="/en/project/8F19006" target="_blank" >8F19006: Development of Novel Ribosome-Targeting Antibiotics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Cell
ISSN
1097-2765
e-ISSN
1097-4164
Volume of the periodical
81
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
3160-3170
UT code for WoS article
000684316300003
EID of the result in the Scopus database
2-s2.0-85111582311