Dataset Information

Non-coding RNAs Potentially Controlling Cell Cycle in the Model Caulobacter crescentus: A Bioinformatic Approach.

ABSTRACT: Caulobacter crescentus represents a remarkable model system to investigate global regulatory programs in bacteria. In particular, several decades of intensive study have revealed that its cell cycle is controlled by a cascade of master regulators, such as DnaA, GcrA, CcrM, and CtrA, that are responsible for the activation of functions required to progress through DNA replication, cell division and morphogenesis of polar structures (flagellum and stalk). In order to accomplish this task, several post-translational (phosphorylation and proteolysis) and transcriptional mechanisms are involved. Surprisingly, the role of non-coding RNAs (ncRNAs) in regulating the cell cycle has not been investigated. Here we describe a bioinformatic analysis that revealed that ncRNAs may well play a crucial role regulating cell cycle in C. crescentus. We used available prediction tools to understand which target genes may be regulated by ncRNAs in this bacterium. Furthermore, we predicted whether ncRNAs with a cell cycle regulated expression profile may be directly regulated by DnaA, GcrA, and CtrA, at the onset, during or end of the S-phase/swarmer cell, or if any of them has CcrM methylation sites in the promoter region. Our analysis suggests the existence of a potentially very important network of ncRNAs regulated by or regulating well-known cell cycle genes in C. crescentus. Our hypothesis is that ncRNAs are intimately connected to the known regulatory network, playing a crucial modulatory role in cell cycle progression.

SUBMITTER: Beroual W

PROVIDER: S-EPMC5988900 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Non-coding RNAs Potentially Controlling Cell Cycle in the Model <i>Caulobacter crescentus</i>: A Bioinformatic Approach.

Beroual Wanassa W Brilli Matteo M Biondi Emanuele G EG

Frontiers in genetics 20180530

<i>Caulobacter crescentus</i> represents a remarkable model system to investigate global regulatory programs in bacteria. In particular, several decades of intensive study have revealed that its cell cycle is controlled by a cascade of master regulators, such as DnaA, GcrA, CcrM, and CtrA, that are responsible for the activation of functions required to progress through DNA replication, cell division and morphogenesis of polar structures (flagellum and stalk). In order to accomplish this task, s ...[more]

PMID: 29899753

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Project description:BackgroundSecond messengers, c-di-GMP and (p)ppGpp, are vital regulatory molecules in bacteria, influencing cellular processes such as biofilm formation, transcription, virulence, quorum sensing, and proliferation. While c-di-GMP and (p)ppGpp are both synthesized from GTP molecules, they play antagonistic roles in regulating the cell cycle. In C. crescentus, c-di-GMP works as a major regulator of pole morphogenesis and cell development. It inhibits cell motility and promotes S-phase entry by inhibiting the activity of the master regulator, CtrA. Intracellular (p)ppGpp accumulates under starvation, which helps bacteria to survive under stressful conditions through regulating nucleotide levels and halting proliferation. (p)ppGpp responds to nitrogen levels through RelA-SpoT homolog enzymes, detecting glutamine concentration using a nitrogen phosphotransferase system (PTS Ntr). This work relates the guanine nucleotide-based second messenger regulatory network with the bacterial PTS Ntr system and investigates how bacteria respond to nutrient availability.ResultsWe propose a mathematical model for the dynamics of c-di-GMP and (p)ppGpp in C. crescentus and analyze how the guanine nucleotide-based second messenger system responds to certain environmental changes communicated through the PTS Ntr system. Our mathematical model consists of seven ODEs describing the dynamics of nucleotides and PTS Ntr enzymes. Our simulations are consistent with experimental observations and suggest, among other predictions, that SpoT can effectively decrease c-di-GMP levels in response to nitrogen starvation just as well as it increases (p)ppGpp levels. Thus, the activity of SpoT (or its homologues in other bacterial species) can likely influence the cell cycle by influencing both c-di-GMP and (p)ppGpp.ConclusionsIn this work, we integrate current knowledge and experimental observations from the literature to formulate a novel mathematical model. We analyze the model and demonstrate how the PTS Ntr system influences (p)ppGpp, c-di-GMP, GMP and GTP concentrations. While this model does not consider all aspects of PTS Ntr signaling, such as cross-talk with the carbon PTS system, here we present our first effort to develop a model of nutrient signaling in C. crescentus.

Dataset Information

Non-coding RNAs Potentially Controlling Cell Cycle in the Model Caulobacter crescentus: A Bioinformatic Approach.

Publications

Non-coding RNAs Potentially Controlling Cell Cycle in the Model <i>Caulobacter crescentus</i>: A Bioinformatic Approach.

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