Bacterial RNA Degradosomes: Molecular Machines under Tight Control

Tejada-Arranz, Alejandro; Crécy‐Lagard, Valérie de; Reuse, Hilde De

doi:10.1016/j.tibs.2019.10.002

Cited by 45 publications

(67 citation statements)

References 104 publications

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“…This study revealed that EZA-resistant mutants of strains SS1 and 26695 also contained mutations that likely affect control of transcription, albeit in different genes. The SS1 mutant had a single amino-acid substitution (Val464Ala) in endoribonuclease RNase Y-an enzyme that regulates the expression of hundreds of genes via processing, stabilization or degradation of their mRNA [23]. In addition, it had a frameshift mutation in the fliO gene, which was shown to be required for transcription of many RpoN (σ54)-and FliA (σ28)-dependent genes in H. pylori [24].…”

Section: Discussionmentioning

confidence: 99%

Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

et al. 2020

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With the rise of bacterial resistance to conventional antibiotics, re-purposing of Food and Drug Administration (FDA) approved drugs currently used to treat non-bacteria related diseases as new leads for antibacterial drug discovery has become an attractive alternative. Ethoxzolamide (EZA), an FDA-approved diuretic acting as a human carbonic anhydrase inhibitor, is known to kill the gastric pathogenic bacterium Helicobacter pylori in vitro via an, as yet, unknown mechanism. To date, EZA activity and resistance have been investigated for only one H. pylori strain, P12. We have now performed a susceptibility and resistance study with H. pylori strains SS1 and 26695. Mutants resistant to EZA were isolated, characterized and their genomes sequenced. Resistance-conferring mutations were confirmed by backcrossing the mutations into the parent strain. As with P12, resistance to EZA in strains SS1 and 26695 does not develop easily, since the rate of spontaneous resistance acquisition was less than 10 −8 . Acquisition of resistance was associated with mutations in 3 genes in strain SS1, and in 6 different genes in strain 26695, indicating that EZA targets multiple systems. All resistant isolates had mutations affecting cell wall synthesis and control of gene expression. EZA's potential for treating duodenal ulcers has already been demonstrated. Our findings suggest that EZA may be developed into a novel anti-H. pylori drug.

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Section: Discussionmentioning

confidence: 99%

Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

et al. 2020

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“…RNA degradosome complexes are composed of two core components: RNases and RNA helicases, while a majority of RNA degradosomes also contain a third core-component, metabolic enzymes (Tables 2 and 3). While most bacteria contain RNase E scaffolded RNA degradosomes, RNases such as RNase J, RNase Y, or PNPase can also form the scaffold of the RNA degradosome in other organisms (Tables 2 and 3) (Durand & Condon, 2018;Szczesny et al, 2012;Tejada-Arranz et al, 2019). Many RNA degradosomes contain both endo-and exo-ribonucleases, while some have only been identified to contain a single nuclease ( Table 2).…”

Section: Compositional Variation Of the Rna Degradosomementioning

confidence: 99%

Phase‐separated bacterial ribonucleoprotein bodies organize mRNA decay

et al. 2020

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In bacteria, mRNA decay is controlled by megadalton scale macromolecular assemblies called, "RNA degradosomes," composed of nucleases and other RNA decay associated proteins. Recent advances in bacterial cell biology have shown that RNA degradosomes can assemble into phase-separated structures, termed bacterial ribonucleoprotein bodies (BR-bodies), with many analogous properties to eukaryotic processing bodies and stress granules. This review will highlight the functional role that BR-bodies play in the mRNA decay process through its organization into a membraneless organelle in the bacterial cytoplasm. This review will also highlight the phylogenetic distribution of BRbodies across bacterial species, which suggests that these phase-separated structures are broadly distributed across bacteria, and in evolutionarily related mitochondria and chloroplasts.

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“…RNases E and Y are the main players in RNA degradation in E. coli and B. subtilis, respectively. Recently, it has been estimated that about 86% of all bacteria contain either RNase E or RNase Y (or, sometimes, both) supporting the broad relevance of these two enzymes (13). While RNase E of E. coli is essential (71), conflicting results concerning the essentiality of RNase Y have been published (18,28,29,37,39).…”

Section: Discussionmentioning

confidence: 99%

“…Theses enzymes can degrade bulk mRNA in a rather unspecific manner, just depending on the accessibility of the RNA molecules as well as perform highly specific cleavages that serve to process an RNA molecule to its mature form. In all organisms, RNA degradation involves an interplay of endo-and exoribonucleases as well as other proteins such as RNA helicases that resolve secondary structures (10,11,12,13). Often, these proteins form a complex called the RNA degradosome.…”

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confidence: 99%

Quasi-essentiality of RNase Y inBacillus subtilisis caused by its critical role in the control of mRNA homeostasis

Benda

Woelfel

Gunka

et al. 2020

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RNA turnover is essential in all domains of life. The endonuclease RNase Y (rny) is one of the key components involved in RNA metabolism of the model organism Bacillus subtilis. Essentiality of RNase Y has been a matter of discussion, since deletion of the rny gene is possible, but leads to severe phenotypic effects. In this work, we demonstrate that the rny mutant strain rapidly evolves suppressor mutations to at least partially alleviate these defects. All suppressor mutants had acquired a duplication of an about 60 kb long genomic region encompassing genes for all three core subunits of the RNA polymerase -α, β, β′. When the duplication of the RNA polymerase genes was prevented by relocation of the rpoA gene in the B. subtilis genome, all suppressor mutants carried distinct single point mutations in evolutionary conserved regions of genes coding either for the β or β' subunits of the RNA polymerase that were not tolerated by wild type bacteria. In vitro transcription assays with the mutated polymerase variants showed massive decreases in transcription efficiency. Altogether, our results suggest a tight cooperation between RNase Y and the RNA polymerase to establish an optimal RNA homeostasis in B. subtilis cells.If the continued activity of a protein may become harmful to the bacteria, it is important not only to prevent expression of the corresponding gene but also to take two important measures: (i) switch off the protein's activity and (ii) degrade the mRNA to exclude further production of the protein. The inactivation or even degradation of proteins is well documented in the model bacteria. For example, in both E. coli and B. subtilis the uptake of toxic ammonium is limited by a regulatory interaction of the ammonium transporter with GlnK, a regulatory protein of the PII family (1,2). Similarly, the uptake of potentially toxic potassium can be prevented by inhibition of potassium transporters at high environmental potassium concentrations, either by the second messenger cyclic di-AMP or by interaction with a dedicated modified signal transduction protein, PtsN (3,4,5). To prevent the accumulation of potentially harmful mRNAs, bacteria rely on a very fast mRNA turnover. Indeed, in E. coli and B. subtilis more than 80% of all transcripts have average half-lives of less than 8 minutes, as compared to about 30 minutes and 10 hours in yeast or human cells, respectively (6,7,8,9). Thus, the mRNA turnover is much faster than the generation time. The high mRNA turnover rate in bacteria contributes to the fast adaptation even in rapidly growing cells. The rapid mRNA turnover is therefore a major factor to resolve the apparent growth speed-adaptation trade-off. 4RNases are the key elements to achieve the rapid mRNA turnover in bacteria. Theses enzymes can degrade bulk mRNA in a rather unspecific manner, just depending on the accessibility of the RNA molecules as well as perform highly specific cleavages that serve to process an RNA molecule to its mature form. In all organisms, RNA degradation involves an interplay ...

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Bacterial RNA Degradosomes: Molecular Machines under Tight Control

Cited by 45 publications

References 104 publications

Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

Phase‐separated bacterial ribonucleoprotein bodies organize mRNA decay

Quasi-essentiality of RNase Y inBacillus subtilisis caused by its critical role in the control of mRNA homeostasis

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