RelA-SpoT Homolog toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis

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dc.contributor.authorBrodiazhenko, Tetiana
dc.contributor.authorAlves Oliveira, Sofia Raquel
dc.contributor.authorRoghanian, Mohammad
dc.contributor.authorSakaguchi, Yuriko
dc.contributor.authorTurnbull, Kathryn Jane
dc.contributor.authorBulvas, Ondrej
dc.contributor.authorTakada, Hiraku
dc.contributor.authorTamman, Hedvig
dc.contributor.authorAinelo, Andres
dc.contributor.authorPohl, Radek
dc.contributor.authorRejman, Dominik
dc.contributor.authorTenson, Tanel
dc.contributor.authorSuzuki, Tsutomu
dc.contributor.authorGarcia-Pino, Abel
dc.contributor.authorAtkinson, Gemma C
dc.contributor.authorHaurilyiuk, Vasili
dc.contributor.authorKurata, Tatsuki
dc.date.accessioned2022-04-28T07:53:34Z
dc.date.available2022-04-28T07:53:34Z
dc.date.issued2021-08
dc.description.abstractRelA-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.et
dc.identifier.urihttps://doi.org/10.1016/j.molcel.2021.06.005
dc.identifier.urihttp://hdl.handle.net/10062/81907
dc.language.isoenget
dc.publisherCell Presset
dc.relationEC/H2020/857518/EU/ WIDESPREAD-2018-03/MIBEstet
dc.relation.ispartofseriesVolume 81, issue 15;
dc.rightsopenAccesset
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectRelA-SpoT Homolog, toxin-antitoxin, tRNA modification, translation, (p)ppGpp(p)ppApp, ribosome, toxSAS, SAS, SAHet
dc.titleRelA-SpoT Homolog toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesiset

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