Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.

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Transcript degradation and codon usage regulate gene expression in a lytic phage

10.1101/647024 ◽

2019 ◽

Author(s):

Benjamin R. Jack ◽

Daniel R. Boutz ◽

Matthew L. Paff ◽

Bartram L. Smith ◽

Claus O. Wilke

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Computational Models ◽

Regulatory Elements ◽

Mechanistic Modeling ◽

Host Cells ◽

Bacteriophage T7 ◽

Lytic Phage ◽

Regulate Gene Expression ◽

Regulate Gene

AbstractMany viral genomes are small, containing only single- or double-digit numbers of genes and relatively few regulatory elements. Yet viruses successfully execute complex regulatory programs as they take over their host cells. Here, we propose that some viruses regulate gene expression via a carefully balanced interplay between transcription, translation, and transcript degradation. As our model system, we employ bacteriophage T7, whose genome of approximately 60 genes is well annotated and for which there is a long history of computational models of gene regulation. We expand upon prior modeling work by implementing a stochastic gene expression simulator that tracks individual transcripts, polymerases, ribosomes, and RNases participating in the transcription, translation, and transcript-degradation processes occurring during a T7 infection. By combining this detailed mechanistic modeling of a phage infection with high throughput gene expression measurements of several strains of bacteriophage T7, evolved and engineered, we can show that both the dynamic interplay between transcription and transcript degradation, and between these two processes and translation, appear to be critical components of T7 gene regulation. Our results point to a generic gene regulation strategy that may have evolved in many other viruses. Further, our results suggest that detailed mechanistic modeling may uncover the biological mechanisms at work in both evolved and engineered virus variants.

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Transcript degradation and codon usage regulate gene expression in a lytic phage†

Virus Evolution ◽

10.1093/ve/vez055 ◽

2019 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Benjamin R Jack ◽

Daniel R Boutz ◽

Matthew L Paff ◽

Bartram L Smith ◽

Claus O Wilke

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Computational Models ◽

Regulatory Elements ◽

Mechanistic Modeling ◽

Host Cells ◽

Bacteriophage T7 ◽

Lytic Phage ◽

Regulate Gene Expression ◽

Regulate Gene

Abstract Many viral genomes are small, containing only single- or double-digit numbers of genes and relatively few regulatory elements. Yet viruses successfully execute complex regulatory programs as they take over their host cells. Here, we propose that some viruses regulate gene expression via a carefully balanced interplay between transcription, translation, and transcript degradation. As our model system, we employ bacteriophage T7, whose genome of approximately sixty genes is well annotated and for which there is a long history of computational models of gene regulation. We expand upon prior modeling work by implementing a stochastic gene expression simulator that tracks individual transcripts, polymerases, ribosomes, and ribonucleases participating in the transcription, translation, and transcript-degradation processes occurring during a T7 infection. By combining this detailed mechanistic modeling of a phage infection with high-throughput gene expression measurements of several strains of bacteriophage T7, evolved and engineered, we can show that both the dynamic interplay between transcription and transcript degradation, and between these two processes and translation, appear to be critical components of T7 gene regulation. Our results point to targeted degradation as a generic gene regulation strategy that may have evolved in many other viruses. Further, our results suggest that detailed mechanistic modeling may uncover the biological mechanisms at work in both evolved and engineered virus variants.

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Roles of M6A Regulators in Hepatocellular Carcinoma: Promotion or Suppression

Current Gene Therapy ◽

10.2174/1566523221666211126105940 ◽

2021 ◽

Vol 21 ◽

Author(s):

Jiamao Chen ◽

Qian Zhang ◽

Ting Liu ◽

Hua Tang

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Binding Proteins ◽

Molecular Mechanisms ◽

Clinical Treatment ◽

Self Renewal ◽

Regulate Gene Expression ◽

Regulate Gene

: Hepatocellular carcinoma (HCC) is the sixth globally diagnosed cancer with a poor prognosis. Although the pathological factors of hepatocellular carcinoma are well elucidated, the underlying molecular mechanisms remain unclear. N6-methyladenosine (m6A) is an adenosine methylation occurring at the N6 site, which is the most prevalent modification of eukaryotic mRNA. Recent studies have shown that m6A can regulate gene expression, thus modulating the processes of cell self-renewal, differentiation, and apoptosis. The methyls in m6A are installed by methyltransferases (“writers”), removed by demethylases (“erasers”) and recognized by m6A-binding proteins (“readers”). In this review, we discuss the roles of above regulators in the progression and prognosis of HCC, and summarize the clinical association between m6A modification and hepatocellular carcinoma, so as to provide more valuable information for clinical treatment.

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Functional Identification of MicroRNA-Centered Complexes in C. Elegans.

10.21203/rs.3.rs-1182303/v1 ◽

2022 ◽

Author(s):

Shilpa Hebbar ◽

Ganesh Panzade ◽

Ajay Vashisht ◽

James Wohlschlegel ◽

Isana Veksler-Lublinsky ◽

...

Keyword(s):

Gene Expression ◽

Binding Proteins ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Mass Spectrometry Analysis ◽

Functional Identification ◽

Regulate Gene Expression ◽

Mutant Phenotypes ◽

Regulate Gene

Abstract microRNAs (miRNAs) are crucial for normal development and physiology. To identify factors that might coordinate with miRNAs to regulate gene expression, we used 2’-O methylated oligonucleotides to precipitate Caenorhabditis elegans let-7, miR-58, and miR-2 miRNAs and the associated proteins. A total of 211 proteins were identified through mass-spectrometry analysis of miRNA co-precipitates, which included previously identified interactors of key miRNA pathway components. Gene ontology analysis of the identified interactors revealed an enrichment for RNA binding proteins, suggesting that we captured proteins that may be involved in mRNA lifecycle. To determine which miRNA interactors are important for miRNA activity, we used RNAi to deplete putative miRNA co-factors in animals with compromised miRNA activity and looked for alterations of the miRNA mutant phenotypes. Depletion of 25 of 39 tested genes modified the miRNA mutant phenotypes in three sensitized backgrounds. Modulators of miRNA phenotypes ranged from RNA binding proteins RBD-1 and CEY-1 to metabolic factors such as DLST-1 and ECH-5, among others. The observed functional interactions suggest widespread coordination of these proteins with miRNAs to ultimately regulate gene expression. This study provides a foundation for future investigations aimed at deciphering the molecular mechanisms of miRNA-mediated gene regulation.

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Genomic decoding of neuronal depolarization by stimulus-specific NPAS4 heterodimers

10.1101/565721 ◽

2019 ◽

Author(s):

G. Stefano Brigidi ◽

Michael G. B. Hayes ◽

Andrea L. Hartzell ◽

Lorane Texari ◽

Pei-Ann Lin ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Transcription Factors ◽

Action Potential ◽

Regulate Gene Expression ◽

Synaptic Inputs ◽

Different Types ◽

Genomic Regulation ◽

External Stimuli ◽

Regulate Gene

SUMMARYCells regulate gene expression in response to salient external stimuli. In neurons, depolarization leads to the expression of inducible transcription factors (ITFs) that direct subsequent gene regulation. Depolarization encodes both a neuron’s action potential (AP) output and synaptic inputs, via excitatory postsynaptic potentials (EPSPs). However, it is unclear if different types of depolarizing signals can be transformed by an ITF into distinct modes of genomic regulation. Here, we show that APs and EPSPs in the murine hippocampus trigger two spatially segregated and molecularly distinct mechanisms that lead to the expression of the ITF NPAS4. These two pathways culminate in the assembly of unique, stimulus-specific NPAS4 heterodimers that exhibit distinctive DNA binding patterns. Thus, NPAS4 independently communicates increases in a neuron’s spiking output and synaptic inputs to the nucleus, enabling gene regulation to be tailored to the type of depolarizing activity experienced by a neuron.

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Gut microbiota has a widespread and modifiable effect on host gene regulation

10.1101/210294 ◽

2017 ◽

Cited By ~ 1

Author(s):

Allison L Richards ◽

Amanda L Muehlbauer ◽

Adnan Alazizi ◽

Michael B Burns ◽

Anthony Findley ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Epithelial Cells ◽

Gut Microbiota ◽

Complex Traits ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Chromatin Accessibility ◽

Host Cells ◽

Host Genes

AbstractVariation in gut microbiome is associated with wellness and disease in humans, yet the molecular mechanisms by which this variation affects the host are not well understood. A likely mechanism is through changing gene regulation in interfacing host epithelial cells. Here, we treated colonic epithelial cells with live microbiota from five healthy individuals and quantified induced changes in transcriptional regulation and chromatin accessibility in host cells. We identified over 5,000 host genes that change expression, including 588 distinct associations between specific taxa and host genes. The taxa with the strongest influence on gene expression alter the response of genes associated with complex traits. Using ATAC-seq, we show that a subset of these changes in gene expression are likely the result of changes in host chromatin accessibility and transcription factor binding induced by exposure to gut microbiota. We then created a manipulated microbial community with titrated doses ofCollinsella, demonstrating that both natural and controlled microbiome composition leads to distinct, and predictable, gene expression profiles in host cells. Together, our results suggest that specific microbes play an important role in regulating expression of individual host genes involved in human complex traits. The ability to fine tune the expression of host genes by manipulating the microbiome suggests future therapeutic routes.

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