Predicting the spread of SARS-CoV-2 variants: An artificial intelligence enabled early detection.

During more than 3 years since its emergence, SARS-CoV-2 has shown great ability to mutate rapidly into diverse variants, some of which turned out to be very infectious and have spread throughout the world causing waves of infections. At this point, many countries have already experienced up to six waves of infections. Extensive academic work has focused on the development of models to predict the pandemic trajectory based on epidemiological data, but none has focused on predicting variant-specific spread.

Balanced cell division is secured by two different regulatory sites in OxyS RNA.

The hydrogen peroxide-induced small RNA OxyS has been proposed to originate from the 3' UTR of a peroxide mRNA. Unexpectedly, phylogenetic OxyS targetome predictions indicate that most OxyS targets belong to the category of "cell cycle," including cell division and cell elongation. Previously, we reported that OxyS inhibits cell division by repressing expression of the essential transcription termination factor , thereby leading to the expression of the KilR protein, which interferes with the function of the major cell division protein, FtsZ.

RelA binding of mRNAs modulates translation or sRNA-mRNA basepairing depending on the position of the GGAG site.

Previously, we reported that RelA protein facilitates Hfq-mediated mRNA-sRNA regulation by binding sRNAs carrying a Shine-Dalgarno-like GGAG sequence. In turn, sRNA-Hfq monomers are stabilized, enabling the attachment of more Hfq subunits to form a functional hexamer. Here, using CLIP-seq, we present a global analysis of RelA-bound RNAs showing that RelA interacts with sRNAs as well as with mRNAs carrying a GGAG motif.

RNA binding of Hfq monomers promotes RelA-mediated hexamerization in a limiting Hfq environment.

The RNA chaperone Hfq, acting as a hexamer, is a known mediator of post-transcriptional regulation, expediting basepairing between small RNAs (sRNAs) and their target mRNAs. However, the intricate details associated with Hfq-RNA biogenesis are still unclear. Previously, we reported that the stringent response regulator, RelA, is a functional partner of Hfq that facilitates Hfq-mediated sRNA-mRNA regulation in vivo and induces Hfq hexamerization in vitro.

mRNA dynamics and alternative conformations adopted under low and high arginine concentrations control polyamine biosynthesis in Salmonella.

Putrescine belongs to the large group of polyamines, an essential class of metabolites that exists throughout all kingdoms of life. The Salmonella speF gene encodes an inducible ornithine decarboxylase that produces putrescine from ornithine. Putrescine can be also synthesized from arginine in a parallel metabolic pathway.

Cross-Regulation between Bacteria and Phages at a Posttranscriptional Level.

The study of bacteriophages (phages) and prophages has provided key insights into almost every cellular process as well as led to the discovery of unexpected new mechanisms and the development of valuable tools. This is exemplified for RNA-based regulation. For instance, the characterization and exploitation of the antiphage CRISPR (clustered regularly interspaced short palindromic repeat) systems is revolutionizing molecular biology.

OxyS small RNA induces cell cycle arrest to allow DNA damage repair.

To maintain genome integrity, organisms employ DNA damage response, the underlying principles of which are conserved from bacteria to humans. The bacterial small RNA OxyS of is induced upon oxidative stress and has been implicated in protecting cells from DNA damage; however, the mechanism by which OxyS confers genome stability remained unknown. Here, we revealed an OxyS-induced molecular checkpoint relay, leading to temporary cell cycle arrest to allow damage repair.

Correction: Gifsy-1 Prophage IsrK with Dual Function as Small and Messenger RNA Modulates Vital Bacterial Machineries.

[This corrects the article DOI: 10.1371/journal.pgen.

Gifsy-1 Prophage IsrK with Dual Function as Small and Messenger RNA Modulates Vital Bacterial Machineries.

While an increasing number of conserved small regulatory RNAs (sRNAs) are known to function in general bacterial physiology, the roles and modes of action of sRNAs from horizontally acquired genomic regions remain little understood. The IsrK sRNA of Gifsy-1 prophage of Salmonella belongs to the latter class. This regulatory RNA exists in two isoforms.

Changes in transcriptional pausing modify the folding dynamics of the pH-responsive RNA element.

Previously, we described a novel pH-responsive RNA element in Escherichia coli that resides in the 5' untranslated region of the alx gene and controls its translation in a pH-dependent manner. Under normal growth conditions, this RNA region forms a translationally inactive structure, but when transcribed under alkaline conditions, it forms an active structure producing the Alx protein. We identified two distinct transcriptional pause sites and proposed that pausing at these sites interfered with the formation of the inactive structure while facilitating folding of the active one.

RelA protein stimulates the activity of RyhB small RNA by acting on RNA-binding protein Hfq.

The conserved RNA-binding protein Hfq and its associated small regulatory RNAs (sRNAs) are increasingly recognized as the players of a large network of posttranscriptional control of gene expression in Gram-negative bacteria. The role of Hfq in this network is to facilitate base pairing between sRNAs and their trans-encoded target mRNAs. Although the number of known sRNA-mRNA interactions has grown steadily, cellular factors that influence Hfq, the mediator of these interactions, have remained unknown.

A pH-responsive riboregulator.

The locus alx, which encodes a putative transporter, was discovered previously in a screen for genes induced under extreme alkaline conditions. Here we show that the RNA region preceding the alx ORF acts as a pH-responsive element, which, in response to high pH, leads to an increase in alx expression. Under normal growth conditions this RNA region forms a translationally inactive structure, but when exposed to high pH, a translationally active structure is formed to produce Alx.

Stochastic analysis of the SOS response in Escherichia coli.

Background: DNA damage in Escherichia coli evokes a response mechanism called the SOS response. The genetic circuit of this mechanism includes the genes recA and lexA, which regulate each other via a mixed feedback loop involving transcriptional regulation and protein-protein interaction. Under normal conditions, recA is transcriptionally repressed by LexA, which also functions as an auto-repressor.

Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule.

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) strains represent a major global health problem. Their virulence is mediated by the concerted activity of an array of virulence factors including toxins, a type III protein secretion system (TTSS), pili, and others. We previously showed that EPEC O127 forms a group 4 capsule (G4C), and in this report we show that EHEC O157 also produces a G4C, whose assembly is dependent on the etp, etk, and wzy genes.

Small RNAs encoded within genetic islands of Salmonella typhimurium show host-induced expression and role in virulence.

The emergence of pathogenic strains of enteric bacteria and their adaptation to unique niches are associated with the acquisition of foreign DNA segments termed 'genetic islands'. We explored these islands for the occurrence of small RNA (sRNA) encoding genes. Previous systematic screens for enteric bacteria sRNAs were mainly carried out using the laboratory strain Escherichia coli K12, leading to the discovery of approximately 80 new sRNA genes.

Regulation of gene expression by small non-coding RNAs: a quantitative view.

The importance of post-transcriptional regulation by small non-coding RNAs has recently been recognized in both pro- and eukaryotes. Small RNAs (sRNAs) regulate gene expression post-transcriptionally by base pairing with the mRNA. Here we use dynamical simulations to characterize this regulation mode in comparison to transcriptional regulation mediated by protein-DNA interaction and to post-translational regulation achieved by protein-protein interaction.

Identification of bacterial small non-coding RNAs: experimental approaches.

Almost 140 bacterial small RNAs (sRNAs; sometimes referred to as non-coding RNAs) have been discovered in the past six years. The majority of these sRNAs were discovered in Escherichia coli, and a smaller subset was characterized in other bacteria, many of which were pathogenic. Many of these genes were identified as a result of systematic screens using computational prediction of sRNAs and experimental-based approaches, including microarray and shotgun cloning.

Differential regulation of Escherichia coli topoisomerase I by Fis.

We previously reported that the P1 promoter of topA encoding topoisomerase I of Escherichia coli is activated in response to oxidative stress, in a Fis-dependent manner. Here we show that Fis regulation of topA varies with the intracellular concentrations of Fis. Thus, when Fis levels are low, hydrogen peroxide treatment results in topA activation, whereas at high Fis levels hydrogen peroxide treatment renders topA P1 inactive.

DeoT, a DeoR-type transcriptional regulator of multiple target genes.

In this study, we investigated the genetic organization and function of Escherichia coli yciT, a gene predicted by computational methods to belong to the DeoR-type family of transcriptional regulators. We show that transcription of yciT (here denoted deoT for deoR-Type) initiates from a promoter located upstream of a putative open reading frame (denoted deoL for deoT Leader). We also show that DeoT acts as a global regulator, repressing the expression of a number of genes involved in a variety of metabolic pathways including transport of maltose, fatty acid beta-oxidation and peptide degradation.

Identification of an Escherichia coli operon required for formation of the O-antigen capsule.

Escherichia coli produces polysaccharide capsules that, based on their mechanisms of synthesis and assembly, have been classified into four groups. The group 4 capsule (G4C) polysaccharide is frequently identical to that of the cognate lipopolysaccharide O side chain and has, therefore, also been termed the O-antigen capsule. The genes involved in the assembly of the group 1, 2, and 3 capsules have been described, but those required for G4C assembly remained obscure.

An abundance of RNA regulators.

The importance of small, noncoding RNAs that act as regulators of transcription, of RNA modification or stability, and of mRNA translation is becoming increasingly apparent. Here we discuss current knowledge of regulatory RNA function and review how the RNAs have been identified in a variety of organisms. Many of the regulatory RNAs act through base-pairing interactions with target RNAs.

The small RNA IstR inhibits synthesis of an SOS-induced toxic peptide.

More than 60 small RNAs (sRNA) have been identified in E. coli. The functions of the majority of these sRNAs are still unclear.

Reliable determination of transposon insertion site in prokaryotes by direct sequencing.

We developed a method to identify the insertion sites of transposons in the chromosome of Salmonella using one step only. In this method, the Salmonella's genomic DNA is directly sequenced using a transposon internal primer. Reliable direct sequencing was achieved using high purity genomic DNA and an improved protocol for automated sequence machine.

A survey of small RNA-encoding genes in Escherichia coli.

Small RNA (sRNA) molecules have gained much interest lately, as recent genome-wide studies have shown that they are widespread in a variety of organisms. The relatively small family of 10 known sRNA-encoding genes in Escherichia coli has been significantly expanded during the past two years with the discovery of 45 novel genes. Most of these genes are still uncharacterized and their cellular roles are unknown.