A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus
Abstract
Small regulatory RNAs (sRNAs) are key drivers of bacterial adaptation to environmental fluctuations, including iron and manganese restriction imposed by the host. This study explored the repertoire of sRNAs produced by the human pathogen Staphylococcus aureus in response to metal limitation. Two sRNAs were identified, S1077 and ZinS, that were regulated by zinc (Zn) availability. Further investigations revealed that, similar to the cnt operon from which it derives, S1077 synthesis is controlled by the transcription factors Zur and Fur. In contrast, zinS transcription is solely repressed by Zur. RNA affinity purification identified several ZinS-associated mRNAs encoding Zn-dependent enzymes, including the alcohol dehydrogenase Adh, whose synthesis is negatively regulated by ZinS. Loss of ZinS does not alter staphylococcal metal accumulation, suggesting a role in a Zn-sparing response. Remarkably, zinS also encodes a small peptide, ZinP. Genomic analysis shows that the regulatory portion of zinS emerged from the 3 untranslated region of zinP and is conserved in S. aureus and closely related species, whereas zinP is also found in phylogenetically distant organisms. Our findings demonstrate that sRNAs facilitate bacterial adaptation to Zn limitation, and that genetic exchange and subsequent neofunctionalization have enabled S. aureus to adapt to metal-restricted environments.
Related
- Cross-regulatory sRNA networks shape adaptive stress responses in Staphylococcus aureus: RsaC and RsaOI regulate galactose metabolism and cell wall homeostasis
- Fgfr3–Wnt signaling crosstalk is involved in maintaining cranial suture integrity
- Mining RNA‐seq data reveals the massive regulon of GcvB small RNA and its physiological significance in maintaining amino acid homeostasis in Escherichia coli
- Integrated multi-omics analysis reveals key genes and metabolic regulatory networks involved in the drought stress response of potato
- Characterization of Ca2+-Dependent SOS-like Pathway Components Involved in the Salt Stress Response of an Intertidal Macroalga, Pyropia haitanensis
BibTeX
@article{charbonnier2026zurdependent,
title = {{A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus}},
author = {Mathilde Charbonnier and Hugo Racine and Samuel Probst-Lotze and Jana N Radin and Gustavo Rios-Delgado and Liangyu Lyu and Hannah M Laster and Maximilian P Kohl and Rafał Mazgaj and Marion Blum and Virginie Marchand and Johana Chicher and Pascale Romby and Stefano Marzi and Isabelle Caldelari and Jai J Tree and Kevin J Waldron and Jeffrey M Boyd and Julien Y Dutheil and Thomas E Kehl-Fie and David Lalaouna},
journal = {Nucleic Acids Research},
year = {2026},
month = sep,
doi = {10.1093/nar/gkag894},
url = {https://hal.science/hal-05780130v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus
AU - Mathilde Charbonnier
AU - Hugo Racine
AU - Samuel Probst-Lotze
AU - Jana N Radin
AU - Gustavo Rios-Delgado
AU - Liangyu Lyu
AU - Hannah M Laster
AU - Maximilian P Kohl
AU - Rafał Mazgaj
AU - Marion Blum
AU - Virginie Marchand
AU - Johana Chicher
AU - Pascale Romby
AU - Stefano Marzi
AU - Isabelle Caldelari
AU - Jai J Tree
AU - Kevin J Waldron
AU - Jeffrey M Boyd
AU - Julien Y Dutheil
AU - Thomas E Kehl-Fie
AU - David Lalaouna
PY - 2026
DA - 2026/09/07
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag894
UR - https://hal.science/hal-05780130v1
AB - Small regulatory RNAs (sRNAs) are key drivers of bacterial adaptation to environmental fluctuations, including iron and manganese restriction imposed by the host. This study explored the repertoire of sRNAs produced by the human pathogen Staphylococcus aureus in response to metal limitation. Two sRNAs were identified, S1077 and ZinS, that were regulated by zinc (Zn) availability. Further investigations revealed that, similar to the cnt operon from which it derives, S1077 synthesis is controlled by the transcription factors Zur and Fur. In contrast, zinS transcription is solely repressed by Zur. RNA affinity purification identified several ZinS-associated mRNAs encoding Zn-dependent enzymes, including the alcohol dehydrogenase Adh, whose synthesis is negatively regulated by ZinS. Loss of ZinS does not alter staphylococcal metal accumulation, suggesting a role in a Zn-sparing response. Remarkably, zinS also encodes a small peptide, ZinP. Genomic analysis shows that the regulatory portion of zinS emerged from the 3 untranslated region of zinP and is conserved in S. aureus and closely related species, whereas zinP is also found in phylogenetically distant organisms. Our findings demonstrate that sRNAs facilitate bacterial adaptation to Zn limitation, and that genetic exchange and subsequent neofunctionalization have enabled S. aureus to adapt to metal-restricted environments.
SN - 0305-1048
SN - 1362-4962
ER -