Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame

Roy, Gauthier; Antoine, Rudy; Schwartz, Annie; Slupek, Stéphanie; Rivera-Millot, Alex; Boudvillain, Marc; Jacob‐Dubuisson, Françoise

doi:10.1128/mbio.00912-22

Cited by 12 publications

(15 citation statements)

References 70 publications

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“…6C ), was recently identified as an upstream ORF (uORF) that post-transcriptionally regulates the production of a TonB-like transporter. However, in the presence of Cu, CruR was suggested to relieve ribosomal stalling (41), unlike CutF that enhances a similar process. Thus, CutF and CruR are apparently not iso-functional.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, Cu-binding to the CutF-like protein B. pertussis CruR (SSN cluster 1) inhibits the production of downstream encoded proteins by a ribosomal stalling-like process. Upon binding of Cu, CruR triggers Rho-dependent transcription termination, preventing the production of the downstream encoded TonB-dependent transporter (41). However, unlike R. capsulatus CutF (SSN cluster 15), CruR activity is Sec signal sequence independent, its C-terminal proline-rich ribosomal stalling-like motif is slightly different, and the cruR-bfgR intergenic region is rather long (162 nucleotides) (41).…”

Section: Discussionmentioning

confidence: 99%

“…Upon binding of Cu, CruR triggers Rho-dependent transcription termination, preventing the production of the downstream encoded TonB-dependent transporter (41). However, unlike R. capsulatus CutF (SSN cluster 15), CruR activity is Sec signal sequence independent, its C-terminal proline-rich ribosomal stalling-like motif is slightly different, and the cruR-bfgR intergenic region is rather long (162 nucleotides) (41). Further, the occurrence of CutF-like proteins without the strict conservation of both the Sec signal peptide and the C-terminal proline-rich ribosomal stalling-like motifs are exemplified by the Cupriavidus metallidurans CzcI and CzcI2 lacking a C-terminal proline-motif (SSN cluster 20).…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted November 12, 2022. ; https://doi.org/10.1101/2022.11.11.516240 doi: bioRxiv preprint independent, its C-terminal proline-rich ribosomal stalling-like motif is slightly different, and the cruR-bfgR intergenic region is rather long (162 nucleotides) (41). Further, the occurrence of CutF-like proteins without the strict conservation of both the Sec signal peptide and the C-terminal proline-rich ribosomal stalling-like motifs are exemplified by the Cupriavidus metallidurans CzcI and CzcI2 lacking a C-terminal proline-motif (SSN cluster 20).…”

Section: The Modes Of Action Of Different Cutf-like Proteins Are Seem...mentioning

confidence: 99%

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Metabolic Sensing of Extra-cytoplasmic Copper Availability via Translational Control by a Nascent Exported Protein

Öztürk

Andrei

Blaby‐Haas

et al. 2022

Preprint

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Metabolic sensing is a crucial prerequisite for cells to adjust their physiology to rapidly changing environments. In bacteria, the response to intra- and extra-cellular ligands is primarily controlled by transcriptional regulators, which activate or repress gene expression to ensure metabolic acclimation. Translational control, such as ribosomal stalling can also contribute to cellular acclimation and has been shown to mediate responses to changing intracellular molecules. In the current study, we demonstrate that co-translational export of the protein CutF regulates translation of the down-stream cutO-encoded multi-copper oxidase CutO in response to extracellular copper (Cu). Our data show that CutF, acting as a Cu sensor, is co-translationally exported by the signal recognition particle pathway. Binding of Cu to the periplasmically exposed Cu-binding motif of CutF delays its co-translational export via its C-terminal ribosome stalling-like motif. This allows the unfolding of an mRNA stem-loop sequence that shields the ribosome-binding site of cutO, which favors its subsequent translation. Bioinformatic analyses reveal that CutF-like proteins are widely distributed in bacteria and often, are located upstream of genes involved in transition metal homeostasis. Our overall findings illustrate a highly conserved control mechanism using co-translational export of a protein acting as a sensor to integrate the changing availability of extracellular nutrients into metabolic acclimation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The Modes Of Action Of Different Cutf-like Proteins Are Seem...mentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Sensing of Extra-cytoplasmic Copper Availability via Translational Control by a Nascent Exported Protein

Öztürk

Andrei

Blaby‐Haas

et al. 2022

Preprint

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“…However, recent research focus on understanding how Bordetella spp. can also modulate virulence in response to other host metabolites ( Gonyar et al, 2019 ) including copper ( Rivera-Millot et al, 2021 ; Roy et al, 2022 ), manganese ( Čapek et al, 2021 ) or glumatate ( Keidel et al, 2018 ).…”

Section: Host Interaction and Colonizationmentioning

confidence: 99%

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

2022

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When bacteria sense cues from the host environment, stress responses are activated. Two component systems, sigma factors, small RNAs, ppGpp stringent response, and chaperones start coordinate the expression of virulence factors or immunomodulators to allow bacteria to respond. Although, some of these are well studied, such as the two-component systems, the contribution of other regulators, such as sigma factors or ppGpp, is increasingly gaining attention. Pseudomonas aeruginosa is the gold standard pathogen for studying the molecular mechanisms to sense and respond to environmental cues. Bordetella spp., on the other hand, is a microbial model for studying host-pathogen interactions at the molecular level. These two pathogens have the ability to colonize the lungs of patients with chronic diseases, suggesting that they have the potential to share a niche and interact. However, the molecular networks that facilitate adaptation of Bordetella spp. to cues are unclear. Here, we offer a side-by-side comparison of what is known about these diverse molecular mechanisms that bacteria utilize to counteract host immune responses, while highlighting the relatively unexplored interactions between them.

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Coping with stress: How bacteria fine-tune protein synthesis and protein transport

Njenga,

Boele,

Öztürk

et al. 2023

Journal of Biological Chemistry

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Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame

Abstract: Copper is a transition metal necessary for living beings but also extremely toxic. Bacteria thus tightly control its homeostasis with transcriptional regulators.

Cited by 12 publications

References 70 publications

Metabolic Sensing of Extra-cytoplasmic Copper Availability via Translational Control by a Nascent Exported Protein

Metabolic Sensing of Extra-cytoplasmic Copper Availability via Translational Control by a Nascent Exported Protein

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

Coping with stress: How bacteria fine-tune protein synthesis and protein transport

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