Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame

Roy, Gauthier; Antoine, Rudy; Schwartz, Annie; Slupek, Stéphanie; Rivera-Millot, Alex; Boudvillain, Marc et Jacob-Dubuisson, Françoise (2022). Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame mBio , vol. 13 , nº 4. pp. 1-17. DOI: 10.1128/mbio.00912-22.

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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 posttranscriptional regulatory mechanisms are yet to be characterized. We identified a three-gene operon, bp2923-bfrG-bp2921, downregulated 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 posttranscriptional 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. IMPORTANCE Copper is a transition metal necessary for living beings but also extremely toxic. Bacteria thus tightly control its homeostasis with transcriptional regulators. In this work, we have identified in the whooping cough agent Bordetella pertussis a new control mechanism mediated by a small protein called CruR, for copper-responsive upstream regulator. While being translated by the ribosome CruR is able to perceive intracellular copper, which shuts down the transcription of downstream genes of the same operon, coding for a copper uptake system. This mechanism limits the import of copper in conditions where it is abundant for the bacterium. This is the first report of “posttranscriptional regulation” in response to copper. Homologs of CruR genes head many operons harboring copper-related genes in various bacteria, and therefore the regulatory function unveiled here is likely a general property of this new protein family. © 2022 Roy et al.

Type de document:	Article
Informations complémentaires:	document: e00912-22
Mots-clés libres:	Bordetella pertussis; DUF2946 family; copper homeostasis; posttranscriptional regulation; upstream ORF.
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	03 févr. 2024 18:42
Dernière modification:	03 févr. 2024 18:42
URI:	https://espace.inrs.ca/id/eprint/13462

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