RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression
Creators
- 1. Kings College London
- 2. University of Edinburgh
- 3. The Infectious and Tropical Disease Institute, Ohio University, Athens
- 4. Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN
- 5. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney
- 6. The Roslin Institute and Edinburgh Infectious Diseases, University of Edinburgh
- 7. MRC Human Genetics Unit, University of Edinburgh
Description
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 in MRSA to identify sRNA-RNA interactions under conditions that mimic the host environment. Using 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 detail on how these contribute to the control of virulence in response to changes in metabolism.
Files
clash-pipelines-master.zip
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Additional details
Funding
- Antibiotic tolerance and small RNA networks in Staphylococcus aureus GNT1139313
- National Health and Medical Research Council
- Understanding bacterial host adaptation to combat infectious disease 201531
- Wellcome Trust
- Edinburgh, Cell Biology. 109093
- Wellcome Trust
- NetRNA – Network of regulatory RNAs across kingdoms and dynamical responses to biotic and abiotic stresses. ANR-10-LABX-0036
- Agence Nationale de la Recherche
- Optimising Innate Host Defence to Combat Antimicrobial Resistance MR/N02995X/1
- UK Research and Innovation
- High resolution metabolite and peptide mass spectrometry 208402
- Wellcome Trust
- Next-Generation RNA Genotype-Phenotype Mapping 207507
- Wellcome Trust
- Unravelling post-transcriptional regulatory networks in pathogenic S. aureus MR/R008205/1
- UK Research and Innovation
- Pathogen diversity, host specificity and virulence BBS/E/D/20002173
- UK Research and Innovation
- IMCBio – Integrative Molecular and Cellular Biology ANR-17-EURE-0023
- Agence Nationale de la Recherche
- Host responses underlying immunity BBS/E/D/20002174
- UK Research and Innovation