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RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression

Author

Listed:
  • Stuart W. McKellar

    (University of Edinburgh)

  • Ivayla Ivanova

    (University of Edinburgh)

  • Pedro Arede

    (University of Edinburgh)

  • Rachel L. Zapf

    (Ohio University)

  • Noémie Mercier

    (Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, UPR9002)

  • Liang-Cui Chu

    (University of Edinburgh)

  • Daniel G. Mediati

    (University of New South Wales)

  • Amy C. Pickering

    (The Roslin Institute and Edinburgh Infectious Diseases, University of Edinburgh, Easter Bush Campus)

  • Paul Briaud

    (Ohio University)

  • Robert G. Foster

    (MRC Human Genetics Unit, University of Edinburgh)

  • Grzegorz Kudla

    (MRC Human Genetics Unit, University of Edinburgh)

  • J. Ross Fitzgerald

    (The Roslin Institute and Edinburgh Infectious Diseases, University of Edinburgh, Easter Bush Campus)

  • Isabelle Caldelari

    (Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, UPR9002)

  • Ronan K. Carroll

    (Ohio University
    The Infectious and Tropical Disease Institute, Ohio University)

  • Jai J. Tree

    (University of New South Wales)

  • Sander Granneman

    (University of Edinburgh)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen responsible for significant human morbidity and mortality. Post-transcriptional regulation by small RNAs (sRNAs) has emerged as an important mechanism for controlling virulence. However, the functionality of the majority of sRNAs during infection is unknown. To address this, we performed UV cross-linking, ligation, and sequencing of hybrids (CLASH) in MRSA to identify sRNA-RNA interactions under conditions that mimic the host environment. Using a double-stranded endoribonuclease III as bait, we uncovered hundreds of novel sRNA-RNA pairs. Strikingly, our results suggest that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. Additionally, we also uncover an sRNA sponging interaction between RsaE and RsaI. Taken together, we present a comprehensive analysis of sRNA-target interactions in MRSA and provide details on how these contribute to the control of virulence in response to changes in metabolism.

Suggested Citation

  • Stuart W. McKellar & Ivayla Ivanova & Pedro Arede & Rachel L. Zapf & Noémie Mercier & Liang-Cui Chu & Daniel G. Mediati & Amy C. Pickering & Paul Briaud & Robert G. Foster & Grzegorz Kudla & J. Ross F, 2022. "RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31173-y
    DOI: 10.1038/s41467-022-31173-y
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    Cited by:

    1. Fabian König & Sarah L. Svensson & Cynthia M. Sharma, 2024. "Interplay of two small RNAs fine-tunes hierarchical flagella gene expression in Campylobacter jejuni," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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