Burning the Candle at Both Ends: Have Exoribonucleases Driven Divergence of Regulatory RNA Mechanisms in Bacteria?

Mediati, Daniel G.; Lalaouna, David; Tree, Jai J.

doi:10.1128/mbio.01041-21

Cited by 13 publications

(9 citation statements)

References 72 publications

(79 reference statements)

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“…Therefore, one would expect the action of RNase III to trigger ftnA mRNA processing, which would provide an mRNA carrying now a 3′ end accessible for PNPase cleavage. This is in agreement with the canonical mechanism of RNA degradation found in the majority of Gram-positive bacteria, which it is initiated by either RNase Y or RNase III and followed by the action of 3′-5′ exoribonucleases such as PNPase and RNase R ( Broglia et al, 2020 ; Mediati et al, 2021 ). Our data indicated that RNase III would process the ftnA mRNA, at least in part, through its 3’UTR ( Figure 3 ).…”

Section: Discussionsupporting

confidence: 89%

Staphylococcus aureus ftnA 3’-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions

et al. 2022

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Iron acquisition and modulation of its intracellular concentration are critical for the development of all living organisms. So far, several proteins have been described to be involved in iron homeostasis. Among them, ferritins act as the major iron storage proteins, sequestering internalized iron and modulating its concentration inside bacterial cells. We previously described that the deletion of the 3’-untranslated region (3’UTR) of the ftnA gene, which codes for ferritin in Staphylococcus aureus, increased the ftnA mRNA and ferritin levels. Here, we show that the ferritin levels are affected by RNase III and PNPase, which target the ftnA 3’UTR. Rifampicin mRNA stability experiments revealed that the half-life of the ftnA mRNA is affected by both RNase III and the ftnA 3’UTR. A transcriptional fusion of the ftnA 3’UTR to the gfp reporter gene decreased green fluorescent protein (GFP) expression, indicating that the ftnA 3’UTR could work as an independent module. Additionally, a chromosomal deletion of the ftnA 3’UTR impaired S. aureus growth under conditions of iron starvation. Overall, this work highlights the biological relevance of the ftnA 3’UTR for iron homeostasis in S. aureus.

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Section: Discussionsupporting

confidence: 89%

Staphylococcus aureus ftnA 3’-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions

et al. 2022

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“…This may be due to the presence of 5′-3′ exoribonuclease activity (RNase J1 and J2) found in Gram-positive Firmicutes , which readily degrades free 3′UTR intermediates and may represent an evolutionary barrier to the evolution of 3′UTR-derived sRNA–mRNA interactions in S. aureus (discussed in ref. 55 ). Regulatory mRNA 3′UTRs like vigR that are protected from processing at the 5′ end is likely a more widespread regulatory mechanism in S. aureus than previously appreciated.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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Treatment of methicillin-resistant Staphylococcus aureus infections is dependent on the efficacy of last-line antibiotics including vancomycin. Treatment failure is commonly linked to isolates with intermediate vancomycin resistance (termed VISA). These isolates have accumulated point mutations that collectively reduce vancomycin sensitivity, often by thickening the cell wall. Changes in regulatory small RNA expression have been correlated with antibiotic stress in VISA isolates however the functions of most RNA regulators is unknown. Here we capture RNA–RNA interactions associated with RNase III using CLASH. RNase III-CLASH uncovers hundreds of novel RNA–RNA interactions in vivo allowing functional characterisation of many sRNAs for the first time. Surprisingly, many mRNA–mRNA interactions are recovered and we find that an mRNA encoding a long 3′ untranslated region (UTR) (termed vigR 3′UTR) functions as a regulatory ‘hub’ within the RNA–RNA interaction network. We demonstrate that the vigR 3′UTR promotes expression of folD and the cell wall lytic transglycosylase isaA through direct mRNA–mRNA base-pairing. Deletion of the vigR 3′UTR re-sensitised VISA to glycopeptide treatment and both isaA and vigR 3′UTR deletions impact cell wall thickness. Our results demonstrate the utility of RNase III-CLASH and indicate that S. aureus uses mRNA-mRNA interactions to co-ordinate gene expression more widely than previously appreciated.

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“…It has been argued in a recent review (Mediati et al . 2021 ) that the smaller number of processed 3′ UTR-derived sRNAs in Gram-positive bacteria might be due to the presence of 5′ → 3′ exoribonucleolytic activity. Specifically, Gram-positive bacteria possess RNase J1, which fully degrades mRNAs from the 5′ end in one go, resulting in fewer stable intermediates for evolution to act on and limiting the development of 3′ UTR-derived sRNAs.…”

Section: Biogenesismentioning

confidence: 99%

An overview of gene regulation in bacteria by small RNAs derived from mRNA 3′ ends

Ponath

Hör

Vogel

2022

FEMS Microbiology Reviews

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Over the past two decades, small non-coding RNAs (sRNAs) that regulate mRNAs by short base pairing have gone from a curiosity to a major class of post-transcriptional regulators in bacteria. They are integral to many stress responses and regulatory circuits, affecting almost all aspects of bacterial life. Following pioneering sRNA searches in the early 2000s, the field quickly focused on conserved sRNA genes in the intergenic regions of bacterial chromosomes. Yet, it soon emerged that there might be another rich source of bacterial sRNAs: processed 3’ end fragments of mRNAs. Several such 3’ end-derived sRNAs have now been characterized, often revealing unexpected, conserved functions in diverse cellular processes. Here, we review our current knowledge of these 3’ end-derived sRNAs: their biogenesis through ribonucleases, their molecular mechanisms, their interactions with RNA-binding proteins, and their functional scope, which range from acting as specialized regulators of single metabolic genes to constituting entire non-coding arms in global stress responses. Recent global RNA interactome studies suggest that the importance of functional 3’ end-derived sRNAs has been vastly underestimated, and that this type of cross-regulation between genes at the mRNA level is more pervasive in bacteria than currently appreciated.

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Burning the Candle at Both Ends: Have Exoribonucleases Driven Divergence of Regulatory RNA Mechanisms in Bacteria?

Cited by 13 publications

References 72 publications

Staphylococcus aureus ftnA 3’-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions

Staphylococcus aureus ftnA 3’-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions

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

An overview of gene regulation in bacteria by small RNAs derived from mRNA 3′ ends

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