RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance

Mediati, Daniel G.; Wong, Julia L.; Gao, Wei; McKellar, Stuart; Pang, Chi Nam Ignatius; Wu, Sylvania; Wu, Winton; Sy, Brandon; Monk, Ian R.; Biazik, Joanna; Wilkins, Marc R.; Howden, Benjamin P; Stinear, Timothy P.; Granneman, Sander; Tree, Jai J.

doi:10.1038/s41467-022-31177-8

Cited by 27 publications

(42 citation statements)

References 74 publications

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“…The two events on dual-function sRNAs are mutually exclusive depending on translation efficiency, RNA stability, and temperature (Aoyama et al , 2021; Raina et al , 2022; Balasubramanian & Vanderpool, 2013; Aoyama et al , 2022). Moreover, post-transcriptional regulation via mRNA-mRNA interactions is not rare in Gram-positive bacteria (Liu et al , 2015; Chen et al , 2015; Ignatov et al , 2020; Mediati et al , 2022).…”

Section: Discussionmentioning

confidence: 99%

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

Miyakoshi

Morita

Kobayashi

et al. 2022

Preprint

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Glutamine synthetase is the key enzyme of nitrogen assimilation, which is encoded in the first cistron of glnALG operon and is induced under nitrogen limiting conditions through transcriptional activation by NtrBC in Salmonella and E. coli. 2-oxoglutarate serves as the carbon skeleton of glutamate and glutamine, but how 2-oxoglutarate fluctuation is controlled in response to nitrogen availability remained unknown. We show that the glnA mRNA produces an Hfq-dependent GlnZ sRNA from its 3′UTR through RNase E-mediated cleavage. Through a base-pairing mechanism, GlnZ primarily regulates sucA, encoding the E1o component of 2-oxoglutarate dehydrogenase. In the cells grown on glutamine as the nitrogen source, the endogenous GlnZ represses the expression of SucA to redirect the carbon flow from the TCA cycle to the nitrogen assimilation pathway. This study also clarifies that the release of GlnZ sRNA from the glnA mRNA by RNase E is essential for the post-transcriptional regulation of sucA, and thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.

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Section: Discussionmentioning

confidence: 99%

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

Miyakoshi

Morita

Kobayashi

et al. 2022

Preprint

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“…Unlike other Gramnegative bacteria, C. jejuni does not encode RNase E, responsible for processing many 3' untranslated region (UTR)-derived sRNAs in Gammaproteobacteria (Miyakoshi et al, 2015;Ponath et al, 2022), and instead encodes RNase Y (Parkhill et al, 2000). Doublestrand-specific RNase III is also emerging as a key player in sRNA processing and regulation (Altuvia et al, 2018;Lioliou et al, 2012;Mediati et al, 2022), and important for ribosomal and CRISPR RNA biogenesis in C. jejuni (Dugar et al, 2018(Dugar et al, , 2013Haddad et al, 2013). We measured CJnc230 expression in total RNA from a panel of RNasedeficient C. jejuni deletion mutant strains by northern blot (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interplay of two small RNAs fine-tunes hierarchical flagellar gene expression in the foodborne pathogenCampylobacter jejuni

König

Svensson

Sharma

2023

Preprint

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Like for many enteric bacteria, flagella are a crucial virulence factor for the foodborne pathogenCampylobacter jejuni, allowing the bacteria to move through the viscous mucus of the human intestine. Assembly of the complex flagellar machinery and filament requires hierarchical regulation via transcriptional control of each component. InC. jejuni, class I genes are transcribed from σ70-dependent promoters and class II/III genes with the help of the alternative sigma factors RpoN (σ54) and FliA (σ28). In contrast to transcriptional control, less is known about post-transcriptional regulation of flagellar biosynthesis cascades via small regulatory RNAs (sRNAs). Here, we characterized two sRNAs with opposing effects on the cascade that fine-tuneC. jejuniflagellar filament assembly and thereby impact motility. We demonstrate that the highly conservedCampylobactersRNA CJnc230 (FlmE, flagellar length and motility enhancer), encoded downstream of the flagellar hook structural protein FlgE, is dependent on RpoN and that RNase III processes CJnc230 from theflgEmRNA, while RNase Y and PNPase mature its 3' end. We identify mRNAs encoding a regulator of flagella-flagella interactions and the anti-σ28factor FlgM as direct targets of CJnc230 repression. Overexpression of CJnc230 de-represses FliA activity and upregulates class III flagellar genes, such as the major flagellinflaA, culminating in longer flagella and increased motility. In contrast, overexpression of the FliA-dependent sRNA CJnc170 (FlmR, flagellar length and motility repressor) reduces flagellar length and motility. Overall, our study demonstrates sRNA-mediated post-transcriptional regulation fine-tunesC. jejuniflagellar biosynthesis through balancing of the hierarchically expressed components.

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“…The two events on dual-function sRNAs are mutually exclusive depending on translation efficiency, RNA stability, and temperature ( Aoyama et al, 2021 ; Raina et al, 2022 ; Balasubramanian and Vanderpool, 2013 ; Aoyama et al, 2022 ). Moreover, post-transcriptional regulation via mRNA-mRNA interactions is not rare in Gram-positive bacteria ( Liu et al, 2015 ; Chen et al, 2015 ; Ignatov et al, 2020 ; Mediati et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae

Miyakoshi

Morita

Kobayashi

et al. 2022

eLife

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Glutamine synthetase (GS) is the key enzyme of nitrogen assimilation induced under nitrogen limiting conditions. The carbon skeleton of glutamate and glutamine, 2-oxoglutarate, is supplied from the TCA cycle, but how this metabolic flow is controlled in response to nitrogen availability remains unknown. We show that the expression of the E1o component of 2-oxoglutarate dehydrogenase, SucA, is repressed under nitrogen limitation in Salmonella enterica and E coli. The repression is exerted at the post-transcriptional level by an Hfq-dependent sRNA GlnZ generated from the 3´UTR of the GS-encoding glnA mRNA. Enterobacterial GlnZ variants contain a conserved seed sequence and primarily regulate sucA through base-pairing far upstream of the translation initiation region. During growth on glutamine as the nitrogen source, the glnA 3´UTR deletion mutants expressed SucA at higher levels than the S. enterica and E. coli wild-type strains, respectively. In E. coli, the transcriptional regulator Nac also participates in the repression of sucA. Lastly, this study clarifies that the release of GlnZ from the glnA mRNA by RNase E is essential for the post-transcriptional regulation of sucA. Thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.

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RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3′UTR required for intermediate vancomycin resistance

Cited by 27 publications

References 74 publications

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance

Interplay of two small RNAs fine-tunes hierarchical flagellar gene expression in the foodborne pathogenCampylobacter jejuni

Glutamine synthetase mRNA releases sRNA from its 3′UTR to regulate carbon/nitrogen metabolic balance in Enterobacteriaceae

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