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

Autor:	Kurata T; Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden. Electronic address: tatsuaki.kurata@med.lu.se., Brodiazhenko T; University of Tartu, Institute of Technology, 50411 Tartu, Estonia., Alves Oliveira SR; University of Tartu, Institute of Technology, 50411 Tartu, Estonia., Roghanian M; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 901 87 Umeå, Sweden; Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen, Denmark., Sakaguchi Y; Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan., Turnbull KJ; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 901 87 Umeå, Sweden; Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen, Denmark., Bulvas O; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovonam. 2, 166 10 Prague 6, Czech Republic., Takada H; Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo, Motoyama, Kita-ku, Kyoto 603-8555, Japan., Tamman H; Cellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Campus La Plaine, Building BC, Room 1C4203, Boulevard du Triomphe, 1050 Brussels, Belgium., Ainelo A; Cellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Campus La Plaine, Building BC, Room 1C4203, Boulevard du Triomphe, 1050 Brussels, Belgium., Pohl R; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovonam. 2, 166 10 Prague 6, Czech Republic., Rejman D; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovonam. 2, 166 10 Prague 6, Czech Republic., Tenson T; University of Tartu, Institute of Technology, 50411 Tartu, Estonia., Suzuki T; Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan., Garcia-Pino A; Cellular and Molecular Microbiology (CM2), Faculté des Sciences, Université Libre de Bruxelles (ULB), Campus La Plaine, Building BC, Room 1C4203, Boulevard du Triomphe, 1050 Brussels, Belgium; WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium., Atkinson GC; Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden. Electronic address: gemma.atkinson@med.lu.se., Hauryliuk V; Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden; University of Tartu, Institute of Technology, 50411 Tartu, Estonia; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, 901 87 Umeå, Sweden. Electronic address: vasili.hauryliuk@med.lu.se.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2021 Aug 05; Vol. 81 (15), pp. 3160-3170.e9. Date of Electronic Publication: 2021 Jun 25.
DOI:	10.1016/j.molcel.2021.06.005
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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