Staphylococcal aconitase expression during iron deficiency is controlled by an sRNA-driven feedforward loop and moonlighting activity
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ABSTRACT:
PROVIDER: PRJEB74242 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12791476.fastq.gz | Fastqsanger.gz | |||
| ERR12791477.fastq.gz | Fastqsanger.gz | |||
| ERR12791478.fastq.gz | Fastqsanger.gz | |||
| ERR12791479.fastq.gz | Fastqsanger.gz | |||
| ERR12791480.fastq.gz | Fastqsanger.gz |
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Project description:Pathogenic bacteria employ complex systems to cope with metal ion shortage conditions and propagate in the host. IsrR is a regulatory RNA (sRNA) whose activity is decisive for optimum Staphylococcus aureus fitness upon iron starvation and for full virulence. IsrR down-regulates several genes encoding iron-containing enzymes to spare iron for essential processes. Here, we report that IsrR regulates the tricarboxylic acid (TCA) cycle by controlling aconitase (CitB), an iron-sulfur cluster-containing enzyme, and its transcriptional regulator, CcpE. This IsrR-dependent dual-regulatory mechanism provides an RNA-driven feedforward loop, underscoring the tight control required to prevent aconitase expression. Beyond its canonical enzymatic role, aconitase becomes an RNA-binding protein with regulatory activity in iron-deprived conditions, a feature that is conserved in S. aureus. Aconitase not only negatively regulates its own expression, but also impacts the enzymes involved in both its substrate supply and product utilization. This moonlighting activity concurrently upregulates pyruvate carboxylase expression, allowing it to compensate for the TCA cycle deficiency associated with iron scarcity. These results highlight the cascade of complex posttranscriptional regulations controlling S. aureus central metabolism in response to iron deficiency.
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Project description:The project is focused on the highly conserved sRNA scr5329 in Streptomyces coelicolor. A proteomics approach revealed that the sRNA regulates several metabolic enzymes, among them the Phosphoenolpyruvate-Carboxykinase (PEPCK), a key enzyme of the central carbon metabolism. The sRNA scr5239 promotes its degradation on the post-transcriptional level. The expression itself is dependent on the global transcriptional regulator DasR, which is N-acetylglucosamine-responsive thereby creating a feedback regulation. By post-transcriptional regulation of PEPCK and likely more targets, scr5239 adds an additional layer to the DasR regulatory network, providing a tool to control the metabolism in dependency to the carbon source.
2020-01-28 | PXD016811 | Pride
Project description:Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
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Project description:Adjustment of cell cycle progression is crucial for bacterial survival and adaptation under adverse conditions. However, the understanding of modulation of cell cycle control in response to environmental changes is rather incomplete. In α-proteobacteria, the broadly conserved cell cycle master regulator CtrA underlies multiple levels of control, including coupling of cell cycle and cell differentiation. CtrA levels are known to be tightly controlled through diverse transcriptional and post-translational mechanisms. Here, small RNA (sRNA)-mediated post-transcriptional regulation is uncovered as an additional level of CtrA fine-tuning. Computational predictions as well as transcriptome and proteome studies consistently suggested targeting of ctrA and the putative cold shock chaperone cspA5 mRNAs by the trans-encoded sRNA (trans-sRNA) GspR (formerly SmelC775) in several Sinorhizobium species. GspR strongly accumulated in the stationary growth phase, especially in minimal medium (MM) cultures. Lack of the gspR locus confers a fitness disadvantage in competition with the wild type, while its overproduction hampers cell growth, suggesting that this riboregulator interferes with cell cycle progression. An eGFP-based reporter in vivo assay, involving wild-type and mutant sRNA and mRNA pairs, experimentally confirmed GspR-dependent post-transcriptional down-regulation of ctrA and cspA5 expression, which most likely occurs through base-pairing to the respective mRNA. The energetically favored secondary structure of GspR is predicted to comprise three stem-loop domains, with stem-loop 1 and stem-loop 3 targeting ctrA and cspA5 mRNA, respectively. Moreover, this work reports evidence for post-transcriptional control of ctrA by CspA5. Thus, this regulation and GspR-mediated post-transcriptional repression of ctrA and cspA5 expression constitute a coherent feed-forward loop, which may enhance the negative effect of GspR on CtrA levels. This novel regulatory circuit involving the riboregulator GspR, CtrA, and a cold shock chaperone may contribute to fine-tuning of ctrA expression.
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Project description:Oxygenic photosynthesis contains multiple proteins that possess Fe2+ or Fe/S complexes as co-factors or prosthetic groups. Accordingly, its composition is heavily re-organized when iron becomes limiting as a nutrient factor, a situation that is frequently encountered in nature. However, the molecular mechanisms controlling the reorganization of the photosynthetic system upon iron deprivation have remained enigmatic. Here we show that the small regulatory RNA IsaR1 (Iron-stress activated RNA 1) plays a pivotal role in acclimation to low iron conditions. The transcription factor Fur cannot facilitate iron starvation dependent repression of it’s targets because it requires iron for DNA binding. We show that the Fur repressed sRNA IsaR1 fulfills this repressor function in iron homeostasis. The IsaR1 regulon consists of at least 15 direct targets, including Fe2+-containing proteins involved in photosynthetic electron transfer, the detoxification of anion radicals, citrate cycle, and in tetrapyrrole biogenesis. We demonstrate that IsaR1 is absolutely necessary to maintain physiological levels of Fe/S cluster biogenesis proteins during iron deprivation. Consequently, IsaR1 affects the acclimation of the photosynthetic apparatus to iron starvation at three levels: (i) directly, via posttranscriptional repression of gene expression and indirectly, (ii) via the suppression of Fe/S cluster co-factor and (iii) pigment biosynthesis. Homologs of IsaR1 are widely conserved throughout the cyanobacterial phylum. We conclude that IsaR1 is a riboregulator of central importance. These findings provide a new perspective for studies of the regulation of iron homeostasis in photosynthetic organisms.
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Project description:We profiled total sRNA and root cell layer specific AGO1-bound sRNA in ktn1 mutant to study the role of KTN1 in miRNA non-cell autonomous activiy in Arabidopsis.
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