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DNA-affinity-purified Chip DAP-chip Method to Determine Gene Targets for Bacterial Two component Regulatory Systems

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Perspectiva mecanística y evolutiva de los homólogos de RelA/SpoT en la señalización de la respuesta estricta y más

Tatsuaki Kurata^1,2, Hiraku Takada^2,3

¹RNA Systems Biochemistry Laboratory, RIKEN Pioneering Research Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Bioscience, biotechnology, and biochemistry

|January 9, 2026

Abstract:

The stringent response is a conserved stress‑adaptation programme in bacteria, mediated by the alarmones (p)ppGpp that reprogramme transcription, translation and metabolism. This mini‑review surveys mechanistic, physiological and evolutionary facets of alarmone signalling across two classes of RelA/SpoT homologue (RSH) enzymes: multi domain-containing long RSHs and small alarmone synthetases/hydrolases (SAS/SAH). We first outline how activation is ribosome‑centred: 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.

Palabras clave:

(p)ppGpp Bacterias evolución de proteínas ribosoma respuesta estricta

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