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Article Dans Une Revue mBio Année : 2022

Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame

Résumé

Copper is essential to most living beings but also highly toxic and as such is an important player at the host-pathogen interface. Bacteria have thus developed homeostatic mechanisms to tightly control its intracellular concentration. Known Cu export and import systems are under transcriptional control, whereas post-transcriptional regulatory mechanisms are yet to be characterized. We identified a three-gene operon, bp2923-bfrG-bp2921, down-regulated by copper and notably encoding a TonB-dependent transporter in Bordetella pertussis. We show here that the protein encoded by the first gene, which is a member of the DUF2946 protein family, represents a new type of upstream Open Reading Frame (uORF) involved in post-transcriptional regulation of the downstream genes. In the absence of copper, the entire operon is transcribed and translated. Perception of copper by the nascent bp2923-coded protein via its conserved CXXC motif triggers Rho-dependent transcription termination between the first and second genes by relieving translation arrest on a conserved C-terminal RAPP motif. Homologs of bp2923 are widespread in bacterial genomes, where they head operons predicted to participate in copper homeostasis. This work has thus unveiled a new mode of genetic regulation by a transition metal and identified a regulatory function for a member of an uncharacterized family of bacterial proteins that we have named CruR, for copper-responsive upstream regulator.
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Dates et versions

hal-03759142 , version 1 (23-08-2022)
hal-03759142 , version 2 (04-10-2022)

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Gauthier Roy, Antoine Rudy, Annie Schwartz, Stéphanie Slupek, Alex Rivera-Millot, et al.. Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame. mBio, 2022, ⟨10.1128/mbio.00912-22⟩. ⟨hal-03759142v2⟩
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