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Mechanistic and evolutionary perspective of RelA/SpoT homologus from and beyond stringent–response singnaling

Kurata, Tatsuaki LU and Takada, Hiraku LU (2026) In Bioscience, Biotechnology and Biochemistry 90(3). p.306-312
Abstract

The stringent response is a conserved stress–adaptation program in bacteria, mediated by the alarmones (p)ppGpp that reprogram transcription, translation, and metabolism. This mini–review surveys mechanistic, physiological, and evolutionary facets of alarmone singnaling across two classes of RelA/SpoT homologue (RSH) enzymes: multidomain-containing long RSHs and small alarmone synthetases/hydrolases (SAS/SAH). We first outline how activation is ribosome–centered: in Escherichia coli, synthesis–only RelA is activated only when bound to a starved (“hungry”) ribosome, while SpoT is hydrolase–biased; in Bacillus subtilis, a single bifunctional Rel shifts from hydrolysis- to synthesis-state when locked on a starved ribosome. Beyond (p)ppGpp,... (More)

The stringent response is a conserved stress–adaptation program in bacteria, mediated by the alarmones (p)ppGpp that reprogram transcription, translation, and metabolism. This mini–review surveys mechanistic, physiological, and evolutionary facets of alarmone singnaling across two classes of RelA/SpoT homologue (RSH) enzymes: multidomain-containing long RSHs and small alarmone synthetases/hydrolases (SAS/SAH). We first outline how activation is ribosome–centered: in Escherichia coli, synthesis–only RelA is activated only when bound to a starved (“hungry”) ribosome, while SpoT is hydrolase–biased; in Bacillus subtilis, a single bifunctional Rel shifts from hydrolysis- to synthesis-state when locked on a starved ribosome. Beyond (p)ppGpp, SAS enzymes diversify outputs by producing adenosine alarmones such as (p)ppApp and, in toxic SAS (toxSAS) modules, by pyrophosphorylating the tRNA 3′–CCA end. Finally, we discuss evolutionary trajectories—from SAH–SAS operons to fused, ribosome–regulated long RSHs—and argue that pseudo–ZFD motifs in some toxSAS likely represent independent acquisitions.

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Contribution to journal
publication status
published
subject
keywords
(p)ppGpp, bacteria, protein evolution, ribosome, stringent response
in
Bioscience, Biotechnology and Biochemistry
volume
90
issue
3
pages
7 pages
publisher
Oxford University Press
external identifiers
  • pmid:41511449
  • scopus:105030927075
ISSN
0916-8451
DOI
10.1093/bbb/zbag003
language
English
LU publication?
yes
id
6498ecb7-8f41-4937-a0d8-010e19b2d778
date added to LUP
2026-04-21 15:20:44
date last changed
2026-07-02 02:09:05
@article{6498ecb7-8f41-4937-a0d8-010e19b2d778,
  abstract     = {{<p>The stringent response is a conserved stress–adaptation program in bacteria, mediated by the alarmones (p)ppGpp that reprogram transcription, translation, and metabolism. This mini–review surveys mechanistic, physiological, and evolutionary facets of alarmone singnaling across two classes of RelA/SpoT homologue (RSH) enzymes: multidomain-containing long RSHs and small alarmone synthetases/hydrolases (SAS/SAH). We first outline how activation is ribosome–centered: in Escherichia coli, synthesis–only RelA is activated only when bound to a starved (“hungry”) ribosome, while SpoT is hydrolase–biased; in Bacillus subtilis, a single bifunctional Rel shifts from hydrolysis- to synthesis-state when locked on a starved ribosome. Beyond (p)ppGpp, SAS enzymes diversify outputs by producing adenosine alarmones such as (p)ppApp and, in toxic SAS (toxSAS) modules, by pyrophosphorylating the tRNA 3′–CCA end. Finally, we discuss evolutionary trajectories—from SAH–SAS operons to fused, ribosome–regulated long RSHs—and argue that pseudo–ZFD motifs in some toxSAS likely represent independent acquisitions.</p>}},
  author       = {{Kurata, Tatsuaki and Takada, Hiraku}},
  issn         = {{0916-8451}},
  keywords     = {{(p)ppGpp; bacteria; protein evolution; ribosome; stringent response}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{306--312}},
  publisher    = {{Oxford University Press}},
  series       = {{Bioscience, Biotechnology and Biochemistry}},
  title        = {{Mechanistic and evolutionary perspective of RelA/SpoT homologus from and beyond stringent–response singnaling}},
  url          = {{http://dx.doi.org/10.1093/bbb/zbag003}},
  doi          = {{10.1093/bbb/zbag003}},
  volume       = {{90}},
  year         = {{2026}},
}