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RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression
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RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression
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Journal Article
RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression
2022
Overview
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.
Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, McKellar et al. apply RNase IIICLASH of multi-drug resistant Staphylococcus aureus under different culture conditions to link the network of RNA-RNA interactions to environmental conditions and find that the production of small membrane-permeabilizing toxins is strongly regulated by sRNAs.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38
/ 49/23
/ 49/39
/ 49/90
/ 49/91
/ 82/29
/ 82/81
/ Baits
/ Biochemistry, Molecular Biology
/ Gene Expression Regulation, Bacterial
/ Humanities and Social Sciences
/ Hybrids
/ Methicillin-Resistant Staphylococcus aureus - genetics
/ Methicillin-Resistant Staphylococcus aureus - metabolism
/ Ribonuclease III - metabolism
/ RNA
/ RNA, Small Untranslated - genetics
/ RNA, Small Untranslated - metabolism
/ Science
/ Toxins
