scholarly journals A Trans-Omics Comparison Reveals Common Gene Expression Strategies in Four Model Organisms and Exposes Similarities and Differences between Them

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 334
Author(s):  
Jaume Forés-Martos ◽  
Anabel Forte ◽  
José García-Martínez ◽  
José E. Pérez-Ortín
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Decay Rates ◽  
Model Organisms ◽  
Minor Role ◽  
Yeast Saccharomyces Cerevisiae ◽  
Degradation Rates ◽  
Gene Expression Control ◽  
Living Organisms ◽  
A Minor

The ultimate goal of gene expression regulation is on the protein level. However, because the amounts of mRNAs and proteins are controlled by their synthesis and degradation rates, the cellular amount of a given protein can be attained by following different strategies. By studying omics data for six expression variables (mRNA and protein amounts, plus their synthesis and decay rates), we previously demonstrated the existence of common expression strategies (CESs) for functionally related genes in the yeast Saccharomyces cerevisiae. Here we extend that study to two other eukaryotes: the yeast Schizosaccharomyces pombe and cultured human HeLa cells. We also use genomic data from the model prokaryote Escherichia coli as an external reference. We show that six-variable profiles (6VPs) can be constructed for every gene and that these 6VPs are similar for genes with similar functions in all the studied organisms. The differences in 6VPs between organisms can be used to establish their phylogenetic relationships. The analysis of the correlations among the six variables supports the hypothesis that most gene expression control occurs in actively growing organisms at the transcription rate level, and that translation plays a minor role. We propose that living organisms use CESs for the genes acting on the same physiological pathways, especially for those belonging to stable macromolecular complexes, but CESs have been modeled by evolution to adapt to the specific life circumstances of each organism.

scholarly journals A trans-omics comparison reveals common gene expression strategies in four model organisms and exposes similarities and differences between them

2020 ◽  
Author(s):  
Jaume Forés-Martos ◽  
Anabel Forte ◽  
José García-Martínez ◽  
José E. Pérez-Ortín
Keyword(s):  
Gene Expression ◽  
Branch Length ◽  
Decay Rates ◽  
Model Organisms ◽  
Minor Role ◽  
Expression Control ◽  
External Reference ◽  
Degradation Rates ◽  
Gene Expression Control ◽  
A Minor

AbstractThe ultimate goal of gene regulation should focus on the protein level. However, as mRNA is an obligate intermediary, and because the amounts of mRNAs and proteins are controlled by their synthesis and degradation rates, the cellular amount of a given protein can be attained following different strategies. By studying omics datasets for six expression variables (mRNA and protein amounts, plus their synthesis and decay rates), we previously demonstrated the existence of common expression strategies (CES) for functionally-related genes in the yeast Saccharomyces cerevisiae. Here we extend that study to two other eukaryotes: the distantly related yeast Schizosaccharomyces pombe and cultured human HeLa cells. We also use genomic datasets from the model prokaryote Escherichia coli as an external reference. We show that CES are also present in all the studied organisms and the differences in them between organisms can be used to establish their phylogenetic relationships. The phenogram based on 6VP has the expected topology for the phylogeny of these four organisms, but shows interesting branch length differences to DNA sequence-based trees.The analysis of the correlations among the six variables supports that most gene expression control occurs in actively growing organisms at the transcription rate level, and that translation plays a minor role in it. We propose that all living cells use CES for the genes acting on the same physiological pathways, especially for those belonging to stable macromolecular complexes, but CES have been modeled by evolution to adapt to the specific life circumstances of each organism. The obtained phenograms may reflect both evolutionary constraints in expression strategies, and lifestyle convergences.

scholarly journals Transcriptional Regulation in Ebola Virus: Effects of Gene Border Structure and Regulatory Elements on Gene Expression and Polymerase Scanning Behavior

2015 ◽  
Vol 90 (4) ◽  
pp. 1898-1909 ◽  
Author(s):  
Kristina Brauburger ◽  
Yannik Boehmann ◽  
Verena Krähling ◽  
Elke Mühlberger
Keyword(s):  
Gene Expression ◽  
Ebola Virus ◽  
Rna Virus ◽  
Regulatory Elements ◽  
Minor Role ◽  
Transcript Levels ◽  
Reading Frame ◽  
Noncoding Regions ◽  
Expression Control ◽  
Gene Expression Control

ABSTRACTThe highly pathogenic Ebola virus (EBOV) has a nonsegmented negative-strand (NNS) RNA genome containing seven genes. The viral genes either are separated by intergenic regions (IRs) of variable length or overlap. The structure of the EBOV gene overlaps is conserved throughout all filovirus genomes and is distinct from that of the overlaps found in other NNS RNA viruses. Here, we analyzed how diverse gene borders and noncoding regions surrounding the gene borders influence transcript levels and govern polymerase behavior during viral transcription. Transcription of overlapping genes in EBOV bicistronic minigenomes followed the stop-start mechanism, similar to that followed by IR-containing gene borders. When the gene overlaps were extended, the EBOV polymerase was able to scan the template in an upstream direction. This polymerase feature seems to be generally conserved among NNS RNA virus polymerases. Analysis of IR-containing gene borders showed that the IR sequence plays only a minor role in transcription regulation. Changes in IR length were generally well tolerated, but specific IR lengths led to a strong decrease in downstream gene expression. Correlation analysis revealed that these effects were largely independent of the surrounding gene borders. Each EBOV gene contains exceptionally long untranslated regions (UTRs) flanking the open reading frame. Our data suggest that the UTRs adjacent to the gene borders are the main regulators of transcript levels. A highly complex interplay between the differentcis-acting elements to modulate transcription was revealed for specific combinations of IRs and UTRs, emphasizing the importance of the noncoding regions in EBOV gene expression control.IMPORTANCEOur data extend those from previous analyses investigating the implication of noncoding regions at the EBOV gene borders for gene expression control. We show that EBOV transcription is regulated in a highly complex yet not easily predictable manner by a set of interactingcis-active elements. These findings are important not only for the design of recombinant filoviruses but also for the design of other replicon systems widely used as surrogate systems to study the filovirus replication cycle under low biosafety levels. Insights into the complex regulation of EBOV transcription conveyed by noncoding sequences will also help to interpret the importance of mutations that have been detected within these regions, including in isolates of the current outbreak.

Nuclear behaviour and cell wall composition in relation to budding in mutants of the yeast Saccharomyces cerevisiae

1986 ◽  
Vol 64 (1) ◽  
pp. 193-200 ◽  
Author(s):  
Mario Lachapelle ◽  
E. Roger Boothroyd
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Spindle Pole ◽  
Minor Role ◽  
Temperature Sensitive ◽  
Yeast Saccharomyces Cerevisiae ◽  
Bud Emergence ◽  
Spindle Elongation ◽  
10 Nm Filaments ◽  
A Minor

A temperature-sensitive, cell division cycle mutant (cdc24–1) and karyogamy-deficient (kar1) mutant of Saccharomyces cerevisiae, both of which can produce binucleate or multinucleate cells, were used to study certain aspects of budding, after fluorescent staining for mannan, chitin, and nuclei (DNA). In most binucleate cells the two nuclei lay close together and divided into the same bud. In a few, however, the nuclei were far apart and one or two buds were formed, each proximal to a nucleus. The proximity of daughter nuclei in most blocked cdc24–1 cells suggests a role for the CDC24 gene product in spindle elongation. The relationship between the nuclei and the number and location of buds supports the theory of a preponderant role for the nucleus in budding. Although buds develop preferentially in regions of low chitin content in kar1 heterokaryons, the ability of cdc24–1 cells to bud even with a uniformly high content of chitin and mannan suggests a minor role for these cell wall constituents in determining the sites of bud emergence. The chitin ring is not needed for bud emergence but seems to play a role in normal bud development and in septum formation. Electron microscopy of cdc24–1 cells blocked (37 °C) for 8 h and released (23 °C) for 30 min showed morphologically normal spindle pole bodies, cytoplasmic microtubules, and intranuclear spindles. Although the chitin ring was absent, the ring of 10-nm filaments was present, consistent with its proposed role in bud emergence.

scholarly journals Investigations into the Structure/Antibacterial Activity Relationships of Cyclam and Cyclen Derivatives

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 224 ◽  
Author(s):  
Luis G. Alves ◽  
João F. Portel ◽  
Sílvia A. Sousa ◽  
Olga Ferreira ◽  
Stephanie Almada ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Chemical Nature ◽  
Critical Parameters ◽  
Model Organisms ◽  
Minor Role ◽  
Bacterial Strains ◽  
Aromatic Rings ◽  
Gram Negative ◽  
A Minor ◽  
Pendant Arms

A series of cyclam- and cyclen-derived salts are described in the present work; they were designed specifically to gain insights into their structure and antibacterial activity towards Staphylococcus aureus and Escherichia coli, used respectively, as Gram-positive and Gram-negative model organisms. The newly synthesized compounds are monosubstituted and trans-disubstituted tetraazamacrocycles that display benzyl, methylbenzyl, trifluoromethylbenzyl, or trifluoroethylbenzyl substituents appended on the nitrogen atoms of the macrocyclic ring. The results obtained show that the chemical nature, polarity, and substitution patterns of the benzyl groups, as well as the number of pendant arms, are critical parameters for the antibacterial activity of the cyclam-based salts. The most active compounds against both bacterial strains were the trans-disubstituted cyclam salts displaying CF3 groups in the para-position of the aromatic rings of the macrocyclic pendant arms. The analogous cyclen species presents a lower activity, revealing that the size of the macrocyclic backbone is an important requirement for the antibacterial activity of the tetraazamacrocycles. The nature of the anionic counterparts present on the salts was found to play a minor role in the antibacterial activity.

scholarly journals The Impact of MicroRNAs on Brain Aging and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Stephan P. Persengiev ◽  
Ivanela I. Kondova ◽  
Ronald E. Bontrop
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Gene Expression Regulation ◽  
Brain Aging ◽  
Functional Decline ◽  
System Level ◽  
Model Organisms ◽  
Small Noncoding Rnas ◽  
The Impact ◽  
Gene Expression Levels

The molecular instructions that govern gene expression regulation are encoded in the genome and ultimately determine the morphology and functional specifications of the human brain. As a consequence, changes in gene expression levels might be directly related to the functional decline associated with brain aging. Small noncoding RNAs, including miRNAs, comprise a group of regulatory molecules that modulate the expression of hundred of genes which play important roles in brain metabolism. Recent comparative studies in humans and nonhuman primates revealed that miRNAs regulate multiple pathways and interconnected signaling cascades that are the basis for the cognitive decline and neurodegenerative disorders during aging. Identifying the roles of miRNAs and their target genes in model organisms combined with system-level studies of the brain would provide more comprehensive understanding of the molecular basis of brain deterioration during the aging process.

scholarly journals The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Maialen Sebastian-delaCruz ◽  
Itziar Gonzalez-Moro ◽  
Ane Olazagoitia-Garmendia ◽  
Ainara Castellanos-Rubio ◽  
Izortze Santin
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Stabilization ◽  
Living Organisms ◽  
Almost All

mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

scholarly journals Gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure

2019 ◽  
Author(s):  
Jan Zrimec ◽  
Filip Buric ◽  
Azam Sheikh Muhammad ◽  
Rhongzen Chen ◽  
Vilhelm Verendel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Model Organisms ◽  
Regulatory Structure ◽  
Expression Levels ◽  
Coding Regions ◽  
Dna Regulatory Motifs ◽  
Gene Regulatory ◽  
The Individual ◽  
Gene Expression Levels

AbstractUnderstanding the genetic regulatory code that governs gene expression is a primary, yet challenging aspiration in molecular biology that opens up possibilities to cure human diseases and solve biotechnology problems. However, the fundamental question of how each of the individual coding and non-coding regions of the gene regulatory structure interact and contribute to the mRNA expression levels remains unanswered. Considering that all the information for gene expression regulation is already present in living cells, here we applied deep learning on over 20,000 mRNA datasets in 7 model organisms ranging from bacteria to Human. We show that in all organisms, mRNA abundance can be predicted directly from the DNA sequence with high accuracy, demonstrating that up to 82% of the variation of gene expression levels is encoded in the gene regulatory structure. Coding and non-coding regions carry both overlapping and orthogonal information and additively contribute to gene expression levels. By searching for DNA regulatory motifs present across the whole gene regulatory structure, we discover that motif interactions can regulate gene expression levels in a range of over three orders of magnitude. The uncovered co-evolution of coding and non-coding regions challenges the current paradigm that single motifs or regions are solely responsible for gene expression levels. Instead, we show that the correct combination of all regulatory regions must be established in order to accurately control gene expression levels. Therefore, the holistic system that spans the entire gene regulatory structure is required to analyse, understand, and design any future gene expression systems.

scholarly journals Methods for the analysis of transcriptome dynamics

2019 ◽  
Vol 8 (5) ◽  
pp. 597-612 ◽  
Author(s):  
Daniela F. Rodrigues ◽  
Vera M. Costa ◽  
Ricardo Silvestre ◽  
Maria L. Bastos ◽  
Félix Carvalho
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Gene Expression Regulation ◽  
System Level ◽  
Rna Transcription ◽  
Expression Control ◽  
Gene Expression Control ◽  
Gene Expression Alterations

Abstract The transcriptome is the complete set of transcripts in a cell or tissue and includes ribosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and regulatory noncoding RNA. At steady-state, the transcriptome results from a compensatory variation of the transcription and decay rate to maintain the RNA concentration constant. RNA transcription constitutes the first stage in gene expression, and thus is a major and primary mode of gene expression control. Nevertheless, regulation of RNA decay is also a key factor in gene expression control, involving either selective RNA stabilization or enhanced degradation. Transcriptome analysis allows the identification of gene expression alterations, providing new insights regarding the pathways and mechanisms involved in physiological and pathological processes. Upon perturbation of cell homeostasis, rapid changes in gene expression are required to adapt to new conditions. Thus, to better understand the regulatory mechanisms associated with gene expression alterations, it is vital to acknowledge the relative contribution of RNA synthesis and decay to the transcriptome. To the toxicology field, the study of gene expression regulation mechanisms can help identify the early and mechanistic relevant cellular events associated with a particular response. This review aims to provide a critical comparison of the available methods used to analyze the contribution of RNA transcription and decay to gene expression dynamics. Notwithstanding, an integration of the data obtained is necessary to understand the entire repercussions of gene transcription changes at a system-level. Thus, a brief overview of the methods available for the integration and analysis of the data obtained from transcriptome analysis will also be provided.

scholarly journals The Pentose Phosphate Pathway in Yeasts–More Than a Poor Cousin of Glycolysis

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 725
Author(s):  
Laura-Katharina Bertels ◽  
Lucía Fernández Murillo ◽  
Jürgen J. Heinisch
Keyword(s):  
Pentose Phosphate Pathway ◽  
Kluyveromyces Lactis ◽  
Aromatic Amino Acids ◽  
Pentose Phosphate ◽  
Minor Role ◽  
Disease Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Key Enzyme ◽  
A Minor ◽  
Glucose 6 Phosphate Dehydrogenase

The pentose phosphate pathway (PPP) is a route that can work in parallel to glycolysis in glucose degradation in most living cells. It has a unidirectional oxidative part with glucose-6-phosphate dehydrogenase as a key enzyme generating NADPH, and a non-oxidative part involving the reversible transketolase and transaldolase reactions, which interchange PPP metabolites with glycolysis. While the oxidative branch is vital to cope with oxidative stress, the non-oxidative branch provides precursors for the synthesis of nucleic, fatty and aromatic amino acids. For glucose catabolism in the baker’s yeast Saccharomyces cerevisiae, where its components were first discovered and extensively studied, the PPP plays only a minor role. In contrast, PPP and glycolysis contribute almost equally to glucose degradation in other yeasts. We here summarize the data available for the PPP enzymes focusing on S. cerevisiae and Kluyveromyces lactis, and describe the phenotypes of gene deletions and the benefits of their overproduction and modification. Reference to other yeasts and to the importance of the PPP in their biotechnological and medical applications is briefly being included. We propose future studies on the PPP in K. lactis to be of special interest for basic science and as a host for the expression of human disease genes.

scholarly journals AnnoMiner is a new web-tool to integrate epigenetics, transcription factor occupancy and transcriptomics data to predict transcriptional regulators

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arno Meiler ◽  
Fabio Marchiano ◽  
Margaux Haering ◽  
Manuela Weitkunat ◽  
Frank Schnorrer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Gene Expression Regulation ◽  
Control Cell ◽  
Transcriptional Regulators ◽  
Model Organisms ◽  
Specific Gene ◽  
Epigenetic Events ◽  
Transcription Factor Occupancy

AbstractGene expression regulation requires precise transcriptional programs, led by transcription factors in combination with epigenetic events. Recent advances in epigenomic and transcriptomic techniques provided insight into different gene regulation mechanisms. However, to date it remains challenging to understand how combinations of transcription factors together with epigenetic events control cell-type specific gene expression. We have developed the AnnoMiner web-server, an innovative and flexible tool to annotate and integrate epigenetic, and transcription factor occupancy data. First, AnnoMiner annotates user-provided peaks with gene features. Second, AnnoMiner can integrate genome binding data from two different transcriptional regulators together with gene features. Third, AnnoMiner offers to explore the transcriptional deregulation of genes nearby, or within a specified genomic region surrounding a user-provided peak. AnnoMiner’s fourth function performs transcription factor or histone modification enrichment analysis for user-provided gene lists by utilizing hundreds of public, high-quality datasets from ENCODE for the model organisms human, mouse, Drosophila and C. elegans. Thus, AnnoMiner can predict transcriptional regulators for a studied process without the strict need for chromatin data from the same process. We compared AnnoMiner to existing tools and experimentally validated several transcriptional regulators predicted by AnnoMiner to indeed contribute to muscle morphogenesis in Drosophila. AnnoMiner is freely available at http://chimborazo.ibdm.univ-mrs.fr/AnnoMiner/.

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