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

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 Fitzgerald, Isabelle Caldelari, Ronan K Carroll, Jai J Tree, Sander Granneman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3560
Pages (from-to)1-20
JournalNature Communications
Volume13
Issue number1
Early online date22 Jun 2022
DOIs
Publication statusPublished - 22 Jun 2022

Keywords

  • Gene Expression Regulation, Bacterial
  • Methicillin-Resistant Staphylococcus aureus/genetics
  • RNA, Bacterial/genetics
  • RNA, Messenger/genetics
  • RNA, Small Untranslated/genetics
  • Ribonuclease III/genetics

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