Comparison of the Essential Cellular Functions of the Two murA Genes of Bacillus anthracis

ABSTRACT Targeted antisense and gene replacement mutagenesis experiments demonstrate that only the murA1 gene and not the murA2 gene is required for the normal cellular growth of Bacillus anthracis. Antisense-based modulation of murA1 gene expression hypersensitizes cells to the MurA-specific antibiotic fosfomycin despite the normally high resistance of B. anthracis to this drug.

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CARP Plays a Key Role in Cellular Growth Under Hypertrophic Stimuli in Neonatal Rat Ventricular Myocytes

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v9i0.3790 ◽

2013 ◽

Vol 9 ◽

Author(s):

Tara A Shrout

Keyword(s):

Gene Expression ◽

Ventricular Myocytes ◽

Cellular Growth ◽

Neonatal Rat ◽

Transcriptional Level ◽

Dual Nature ◽

Hypertrophic Growth ◽

Rat Ventricular Myocytes ◽

Neonatal Rat Ventricular Myocytes ◽

Over Time

Cardiac hypertrophy is a growth process that occurs in response to stress stimuli or injury, and leads to the induction of several pathways to alter gene expression. Under hypertrophic stimuli, sarcomeric structure is disrupted, both as a consequence of gene expression and local changes in sarcomeric proteins. Cardiac-restricted ankyrin repeat protein (CARP) is one such protein that function both in cardiac sarcomeres and at the transcriptional level. We postulate that due to this dual nature, CARP plays a key role in maintaining the cardiac sarcomere. GATA4 is another protein detected in cardiomyocytes as important in hypertrophy, as it is activated by hypertrophic stimuli, and directly binds to DNA to alter gene expression. Results of GATA4 activation over time were inconclusive; however, the role of CARP in mediating hypertrophic growth in cardiomyocytes was clearly demonstrated. In this study, Neonatal Rat Ventricular Myocytes were used as a model to detect changes over time in CARP and GATA4 under hypertrophic stimulation by phenylephrine and high serum media. Results were detected by analysis of immunoblotting. The specific role that CARP plays in mediating cellular growth under hypertrophic stimuli was studied through immunofluorescence, which demonstrated that cardiomyocyte growth with hypertrophic stimulation was significantly blunted when NRVMs were co-treated with CARP siRNA. These data suggest that CARP plays an important role in the hypertrophic response in cardiomyocytes.

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Commuting to Work: Nucleolar Long Non-Coding RNA Control Ribosome Biogenesis from Near and Far

Non-Coding RNA ◽

10.3390/ncrna7030042 ◽

2021 ◽

Vol 7 (3) ◽

pp. 42

Author(s):

Victoria Mamontova ◽

Barbara Trifault ◽

Lea Boten ◽

Kaspar Burger

Keyword(s):

Gene Expression ◽

Rna Polymerase Ii ◽

Ribosome Biogenesis ◽

Intergenic Spacer ◽

Cellular Growth ◽

Rrna Synthesis ◽

Protein Coding ◽

Non Coding Rna ◽

And Function ◽

In Cis

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.

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Unearthing LTR retrotransposon gag genes co-opted in the deep evolution of eukaryotes

Molecular Biology and Evolution ◽

10.1093/molbev/msab101 ◽

2021 ◽

Author(s):

Jianhua Wang ◽

Guan-Zhu Han

Keyword(s):

Gene Expression ◽

Selective Pressure ◽

Ltr Retrotransposon ◽

Ltr Retrotransposons ◽

Cellular Functions ◽

The Family ◽

Family Level ◽

Gene Expression Analyses ◽

Comprehensive Picture ◽

Gypsy Retrotransposons

Abstract LTR retrotransposons comprise a major component of the genomes of eukaryotes. On occasion, retrotransposon genes can be recruited by their hosts for diverse functions, a process formally referred to as co-option. However, a comprehensive picture of LTR retrotransposon gag gene co-option in eukaryotes is still lacking, with several documented cases exclusively involving Ty3/Gypsy retrotransposons in animals. Here we use a phylogenomic approach to systemically unearth co-option of retrotransposon gag genes above the family level of taxonomy in 2,011 eukaryotes, namely co-option occurring during the deep evolution of eukaryotes. We identify a total of 14 independent gag gene co-option events across more than 740 eukaryote families, eight of which have not been reported previously. Among these retrotransposon gag gene co-option events, nine, four, and one involve gag genes of Ty3/Gypsy, Ty1/Copia, and Bel-Pao retrotransposons, respectively. Seven, four, and three co-option events occurred in animals, plants, and fungi, respectively. Interestingly, two co-option events took place in the early evolution of angiosperms. Both selective pressure and gene expression analyses further support that these co-opted gag genes might perform diverse cellular functions in their hosts, and several co-opted gag genes might be subject to positive selection. Taken together, our results provide a comprehensive picture of LTR retrotransposon gag gene co-option events that occurred during the deep evolution of eukaryotes, and suggest paucity of LTR retrotransposon gag gene co-option during the deep evolution of eukaryotes.

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Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay

Molecular and Cellular Biology ◽

10.1128/mcb.00361-08 ◽

2008 ◽

Vol 28 (13) ◽

pp. 4320-4330 ◽

Cited By ~ 126

Author(s):

Arneet L. Saltzman ◽

Yoon Ki Kim ◽

Qun Pan ◽

Matthew M. Fagnani ◽

Lynne E. Maquat ◽

...

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Mrna Decay ◽

Splice Variants ◽

Cellular Functions ◽

Regulate Gene Expression ◽

Premature Termination Codons ◽

Microarray Profiling ◽

Nonsense Mediated Mrna Decay ◽

Regulate Gene

ABSTRACT Alternative splicing (AS) can regulate gene expression by introducing premature termination codons (PTCs) into spliced mRNA that subsequently elicit transcript degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the range of cellular functions controlled by this process and the factors required are poorly understood. By quantitative AS microarray profiling, we find that there are significant overlaps among the sets of PTC-introducing AS events affected by individual knockdown of the three core human NMD factors, Up-Frameshift 1 (UPF1), UPF2, and UPF3X/B. However, the levels of some PTC-containing splice variants are less or not detectably affected by the knockdown of UPF2 and/or UPF3X, compared with the knockdown of UPF1. The intron sequences flanking the affected alternative exons are often highly conserved, suggesting important regulatory roles for these AS events. The corresponding genes represent diverse cellular functions, and surprisingly, many encode core spliceosomal proteins and assembly factors. We further show that conserved, PTC-introducing AS events are enriched in genes that encode core spliceosomal proteins. Where tested, altering the expression levels of these core spliceosomal components affects the regulation of PTC-containing splice variants from the corresponding genes. Together, our results show that AS-coupled NMD can have different UPF factor requirements and is likely to regulate many general components of the spliceosome. The results further implicate general spliceosomal components in AS regulation.

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Bivalent Genes Targeting of Glioma Heterogeneity and Plasticity

International Journal of Molecular Sciences ◽

10.3390/ijms22020540 ◽

2021 ◽

Vol 22 (2) ◽

pp. 540

Author(s):

Mariam Markouli ◽

Dimitrios Strepkos ◽

Kostas A. Papavassiliou ◽

Athanasios G. Papavassiliou ◽

Christina Piperi

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Integration Site ◽

Survival Rates ◽

Family Members ◽

Therapy Resistance ◽

Cellular Functions ◽

Cns Neoplasms ◽

Development Regulation

Gliomas account for most primary Central Nervous System (CNS) neoplasms, characterized by high aggressiveness and low survival rates. Despite the immense research efforts, there is a small improvement in glioma survival rates, mostly attributed to their heterogeneity and complex pathophysiology. Recent data indicate the delicate interplay of genetic and epigenetic mechanisms in regulating gene expression and cell differentiation, pointing towards the pivotal role of bivalent genes. Bivalency refers to a property of chromatin to acquire more than one histone marks during the cell cycle and rapidly transition gene expression from an active to a suppressed transcriptional state. Although first identified in embryonal stem cells, bivalent genes have now been associated with tumorigenesis and cancer progression. Emerging evidence indicates the implication of bivalent gene regulation in glioma heterogeneity and plasticity, mainly involving Homeobox genes, Wingless-Type MMTV Integration Site Family Members, Hedgehog protein, and Solute Carrier Family members. These genes control a wide variety of cellular functions, including cellular differentiation during early organism development, regulation of cell growth, invasion, migration, angiogenesis, therapy resistance, and apoptosis. In this review, we discuss the implication of bivalent genes in glioma pathogenesis and their potential therapeutic targeting options.

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Minireview: Transcriptional Regulation in Development of Bone

Endocrinology ◽

10.1210/en.2004-1343 ◽

2005 ◽

Vol 146 (3) ◽

pp. 1012-1017 ◽

Cited By ~ 108

Author(s):

Tatsuya Kobayashi ◽

Henry Kronenberg

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Transcription Factors ◽

Bone Cells ◽

Genetic Manipulation ◽

Bone Development ◽

Regulation Of Gene Expression ◽

Bone Cell ◽

Cellular Functions ◽

Multiple Differentiation

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.

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Cadmium-associated differential methylation throughout the placental genome: epigenome-wide association study of two US birth cohorts

10.1101/130286 ◽

2017 ◽

Cited By ~ 1

Author(s):

Todd M. Everson ◽

Tracy Punshon ◽

Brian P. Jackson ◽

Ke Hao ◽

Luca Lambertini ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Fetal Development ◽

Meta Analysis ◽

Reproductive Toxicity ◽

Differential Methylation ◽

Cellular Growth ◽

Birth Cohorts ◽

Inflammatory Signaling ◽

P Values

AbstractBackgroundCadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.MethodsUsing placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.ResultsWe identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7, and lower expression of RORA, were associated with lower birth weight z-scores (p-values < 0.05).ConclusionCd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.SignificanceCadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.

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The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex

Nucleic Acids Research ◽

10.1093/nar/gkab739 ◽

2021 ◽

Author(s):

Subramaniyam Ravichandran ◽

Maria Razzaq ◽

Nazia Parveen ◽

Ambarnil Ghosh ◽

Kyeong Kyu Kim

Keyword(s):

Gene Expression ◽

Rna Structure ◽

Biological Significance ◽

Cellular Functions ◽

Hairpin Loops ◽

G Quadruplex ◽

Reporter Assays ◽

Expression Activity ◽

The Stability ◽

And Function

Abstract G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

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Angiotensin II early regulated genes in H295R human adrenocortical cells

Physiological Genomics ◽

10.1152/physiolgenomics.00097.2004 ◽

2004 ◽

Vol 19 (1) ◽

pp. 106-116 ◽

Cited By ~ 43

Author(s):

Damian G. Romero ◽

Maria Plonczynski ◽

Gaston R. Vergara ◽

Elise P. Gomez-Sanchez ◽

Celso E. Gomez-Sanchez

Keyword(s):

Gene Expression ◽

Angiotensin Ii ◽

Intracellular Signaling ◽

Zona Glomerulosa ◽

Ang Ii ◽

Cellular Functions ◽

Cellular Mechanisms ◽

Mediated Effects ◽

Aldosterone Production ◽

H295r Cells

Evidence for the dysregulation of aldosterone synthesis in cardiovascular pathophysiology has renewed interest in the control of its production. Cellular mechanisms by which angiotensin II (ANG II) stimulates aldosterone synthesis in the adrenal zona glomerulosa are incompletely understood. To elucidate the mechanism of intracellular signaling by ANG II stimulation in the adrenal, we have studied immediate-early regulated genes in human adrenal H295R cells using cDNA microarrays. H295R cells were stimulated with ANG II for 3 h. Gene expression was analyzed by microarray technology and validated by real-time RT-PCR. Eleven genes were found to be upregulated by ANG II. These encode the proteins for ferredoxin, Nor1, Nurr1, c6orf37, CAT-1, A20, MBLL, M-Ras, RhoB, GADD45α, and a novel protein designated FLJ45273 . Maximum expression levels for all genes occurred 3–6 h after ANG II stimulation. This increase was dose dependent and preceded maximal aldosterone production. Other aldosterone secretagogues, K+and endothelin-1 (ET-1), also induced the expression of these genes with variable efficiency depending on the gene and with lower potency than ANG II. ACTH had negligible effect on gene expression except for the CAT-1 and Nurr1 genes. These ANG II-stimulated genes are involved in several cellular functions and are good candidate effectors and regulators of ANG II-mediated effects in adrenal zona glomerulosa.

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SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program

eLife ◽

10.7554/elife.37419 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 18

Author(s):

Madara Ratnadiwakara ◽

Stuart K Archer ◽

Craig I Dent ◽

Igor Ruiz De Los Mozos ◽

Traude H Beilharz ◽

...

Keyword(s):

Gene Expression ◽

Cellular Functions ◽

Protein Levels ◽

The Core ◽

Molecular Events ◽

Coordinate Gene Expression ◽

Pluripotency Gene ◽

Steady State Levels ◽

Expression Program ◽

Pluripotency Genes

The establishment and maintenance of pluripotency depend on precise coordination of gene expression. We establish serine-arginine-rich splicing factor 3 (SRSF3) as an essential regulator of RNAs encoding key components of the mouse pluripotency circuitry, SRSF3 ablation resulting in the loss of pluripotency and its overexpression enhancing reprogramming. Strikingly, SRSF3 binds to the core pluripotency transcription factor Nanog mRNA to facilitate its nucleo-cytoplasmic export independent of splicing. In the absence of SRSF3 binding, Nanog mRNA is sequestered in the nucleus and protein levels are severely downregulated. Moreover, SRSF3 controls the alternative splicing of the export factor Nxf1 and RNA regulators with established roles in pluripotency, and the steady-state levels of mRNAs encoding chromatin modifiers. Our investigation links molecular events to cellular functions by demonstrating how SRSF3 regulates the pluripotency genes and uncovers SRSF3-RNA interactions as a critical means to coordinate gene expression during reprogramming, stem cell self-renewal and early development.

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