ArticlePLoS biology2020
How the initiating ribosome copes with ppGpp to translate mRNAs.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- The alarmone pGpp inhibits translation through GTP depletion.Nucleic acids research · 2026Article
- Structural Basis of pppGpp Binding to the N-Terminal Domain of the Bifunctional RelA/SpoT Homolog RelInternational journal of molecular sciences · 2026Article
- A Microscale Platform for the Comprehensive Analysis of Bacterial Translation Initiation.International journal of molecular sciences · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- The stringent response does not influence ribosome pausing in Bacillus subtilis.Nucleic acids research · 2025Article
- DNA aptamer AptScientific reports · 2025Article
- Integrated transcriptomics and metabolomics reveal multi-target mechanisms of tannins against Clostridium perfringens and necrotic enteritis.Journal of animal science and biotechnology · 2025Article
- Structural and mechanistic basis for the regulation of the chloroplast signal recognition particle by (p)ppGpp.FEBS letters · 2025Article
- Shaping of microbial phenotypes by trade-offs.Nature communications · 2024Review
- An easy tool to monitor the elemental steps of in vitro translation via gel electrophoresis of fluorescently labeled small peptides.RNA (New York, N.Y.) · 2024Article
- At the Crossroad of Nucleotide Dynamics and Protein Synthesis in Bacteria.Microbiology and molecular biology reviews : MMBR · 2023Review
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- Gut colonization by Bacteroides requires translation by an EF-G paralog lacking GTPase activity.The EMBO journal · 2023Article
- Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin.Nucleic acids research · 2023Article
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Recent functional insights into the magic role of (p)ppGpp in growth control.Computational and structural biotechnology journal · 2023Review
- Expression of Bacillus subtilis ABCF antibiotic resistance factor VmlR is regulated by RNA polymerase pausing, transcription attenuation, translation attenuation and (p)ppGpp.Nucleic acids research · 2022Article
- Cellular perception of growth rate and the mechanistic origin of bacterial growth law.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation.PLoS genetics · 2022Article
- Ribosomal protein S18 acetyltransferase RimI is responsible for the acetylation of elongation factor Tu.The Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During host colonization, bacteria use the alarmones (p)ppGpp to reshape their proteome by acting pleiotropically on DNA, RNA, and protein synthesis. Here, we elucidate how the initiating ribosome senses the cellular pool of guanosine nucleotides and regulates the progression towards protein synthesis. Our results show that the affinity of guanosine triphosphate (GTP) and the inhibitory concentration of ppGpp for the 30S-bound initiation factor IF2 vary depending on the programmed mRNA. The TufA mRNA enhanced GTP affinity for 30S complexes, resulting in improved ppGpp tolerance and allowing efficient protein synthesis. Conversely, the InfA mRNA allowed ppGpp to compete with GTP for IF2, thus stalling 30S complexes. Structural modeling and biochemical analysis of the TufA mRNA unveiled a structured enhancer of translation initiation (SETI) composed of two consecutive hairpins proximal to the translation initiation region (TIR) that largely account for ppGpp tolerance under physiological concentrations of guanosine nucleotides. Furthermore, our results show that the mechanism enhancing ppGpp tolerance is not restricted to the TufA mRNA, as similar ppGpp tolerance was found for the SETI-containing Rnr mRNA. Finally, we show that IF2 can use pppGpp to promote the formation of 30S initiation complexes (ICs), albeit requiring higher factor concentration and resulting in slower transitions to translation elongation. Altogether, our data unveil a novel regulatory mechanism at the onset of protein synthesis that tolerates physiological concentrations of ppGpp and that bacteria can exploit to modulate their proteome as a function of the nutritional shift happening during stringent response and infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.