From magic spot ppGpp to MESH1: Stringent response from bacteria to metazoa

Chi, Jen‐Tsan; Zhou, Pei

doi:10.1371/journal.ppat.1011105

Cited by 3 publications

(2 citation statements)

References 33 publications

(51 reference statements)

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“…When expressed recombinantly, the MESH1 protein functionally partially complemented SpoT-deficiency in bacteria and suppressed RelA-induced inhibition of cell growth, the mechanism of which has not been resolved [ 11 ]. Drosophila with deleted Mesh1 gene exhibited stunted body growth and sensitivity to starvation.…”

Section: Metazoan ‘Stringent-like Response’mentioning

confidence: 99%

“…Accumulated evidence suggests that the stress response entails a large web of regulatory circuits, perhaps underscoring its importance in cellular and organismic persistence. As indicated earlier, our knowledge on (p)ppGpp derives overwhelmingly from bacteria (mainly E. coli and B. subtilis ), although limited evidence of these nucleotides in selected metazoa (such as Drosophila , lower plants, and human) has emerged recently [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The Archaea is generally considered devoid of a canonical stringent response, as the search for (p)ppGpp in this kingdom has produced conflicting results [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

Barik¹

2023

IJMS

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The stringent response, originally identified in Escherichia coli as a signal that leads to reprogramming of gene expression under starvation or nutrient deprivation, is now recognized as ubiquitous in all bacteria, and also as part of a broader survival strategy in diverse, other stress conditions. Much of our insight into this phenomenon derives from the role of hyperphosphorylated guanosine derivatives (pppGpp, ppGpp, pGpp; guanosine penta-, tetra- and tri-phosphate, respectively) that are synthesized on starvation cues and act as messengers or alarmones. These molecules, collectively referred to here as (p)ppGpp, orchestrate a complex network of biochemical steps that eventually lead to the repression of stable RNA synthesis, growth, and cell division, while promoting amino acid biosynthesis, survival, persistence, and virulence. In this analytical review, we summarize the mechanism of the major signaling pathways in the stringent response, consisting of the synthesis of the (p)ppGpp, their interaction with RNA polymerase, and diverse factors of macromolecular biosynthesis, leading to differential inhibition and activation of specific promoters. We also briefly touch upon the recently reported stringent-like response in a few eukaryotes, which is a very disparate mechanism involving MESH1 (Metazoan SpoT Homolog 1), a cytosolic NADPH phosphatase. Lastly, using ppGpp as an example, we speculate on possible pathways of simultaneous evolution of alarmones and their multiple targets.

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Section: Metazoan ‘Stringent-like Response’mentioning

confidence: 99%