Expression of genes encoding peroxisomal proteins in Saccharomyces cerevisiae is regulated by different circuits of transcriptional control

The mammalian myocardium is an omnivorous organ that relies on multiple substrates in order to fulfill its tremendous energy demands. Cardiac energy metabolism preference is regulated at several critical points, including at the level of gene transcription. Emerging evidence indicates that the nuclear receptor PPARαand its cardiac-enriched coactivator protein, PGC-1α, play important roles in the transcriptional control of myocardial energy metabolism. The PPARα-PGC-1αcomplex controls the expression of genes encoding enzymes involved in cardiac fatty acid and glucose metabolism as well as mitochondrial biogenesis. Also, evidence has emerged that the activity of the PPARα-PGC-1αcomplex is perturbed in several pathophysiologic conditions and that altered activity of this pathway may play a role in cardiomyopathic remodeling. In this review, we detail the current understanding of the effects of the PPARα-PGC-1αaxis in regulating mitochondrial energy metabolism and cardiac function in response to physiologic and pathophysiologic stimuli.

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mRNAs Encoding Telomerase Components and Regulators Are Controlled by UPF Genes in Saccharomyces cerevisiae

Eukaryotic Cell ◽

10.1128/ec.2.1.134-142.2003 ◽

2003 ◽

Vol 2 (1) ◽

pp. 134-142 ◽

Cited By ~ 50

Author(s):

Jeffrey N. Dahlseid ◽

Jodi Lew-Smith ◽

Michael J. Lelivelt ◽

Shinichiro Enomoto ◽

Amanda Ford ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Telomere Length ◽

Dna Sequences ◽

Mrna Levels ◽

Loss Of Function ◽

Telomeric Silencing ◽

Expression Of Genes ◽

Mutant Strains ◽

Genes Encoding

ABSTRACT Telomeres, the chromosome ends, are maintained by a balance of activities that erode and replace the terminal DNA sequences. Furthermore, telomere-proximal genes are often silenced in an epigenetic manner. In Saccharomyces cerevisiae, average telomere length and telomeric silencing are reduced by loss of function of UPF genes required in the nonsense-mediated mRNA decay (NMD) pathway. Because NMD controls the mRNA levels of several hundred wild-type genes, we tested the hypothesis that NMD affects the expression of genes important for telomere functions. In upf mutants, high-density oligonucleotide microarrays and Northern blots revealed that the levels of mRNAs were increased for genes encoding the telomerase catalytic subunit (Est2p), in vivo regulators of telomerase (Est1p, Est3p, Stn1p, and Ten1p), and proteins that affect telomeric chromatin structure (Sas2p and Orc5p). We investigated whether overexpressing these genes could mimic the telomere length and telomeric silencing phenotypes seen previously in upf mutant strains. Increased dosage of STN1, especially in combination with increased dosage of TEN1, resulted in reduced telomere length that was indistinguishable from that in upf mutants. Increased levels of STN1 together with EST2 resulted in reduced telomeric silencing like that of upf mutants. The half-life of STN1 mRNA was not altered in upf mutant strains, suggesting that an NMD-controlled transcription factor regulates the levels of STN1 mRNA. Together, these results suggest that NMD maintains the balance of gene products that control telomere length and telomeric silencing primarily by maintaining appropriate levels of STN1, TEN1, and EST2 mRNA.

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Glucose as a hormone: receptor-mediated glucose sensing in the yeast Saccharomyces cerevisiae

Biochemical Society Transactions ◽

10.1042/bst0330247 ◽

2005 ◽

Vol 33 (1) ◽

pp. 247-252 ◽

Cited By ~ 74

Author(s):

M. Johnston ◽

J.-H. Kim

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Signal Transduction Pathway ◽

Glucose Transporters ◽

Glucose Sensing ◽

Yeast Cells ◽

Transduction Pathway ◽

Yeast Saccharomyces Cerevisiae ◽

Expression Of Genes ◽

Genes Encoding

Because glucose is the principal carbon and energy source for most cells, most organisms have evolved numerous and sophisticated mechanisms for sensing glucose and responding to it appropriately. This is especially apparent in the yeast Saccharomyces cerevisiae, where these regulatory mechanisms determine the distinctive fermentative metabolism of yeast, a lifestyle it shares with many kinds of tumour cells. Because energy generation by fermentation of glucose is inefficient, yeast cells must vigorously metabolize glucose. They do this, in part, by carefully regulating the first, rate-limiting step of glucose utilization: its transport. Yeast cells have learned how to sense the amount of glucose that is available and respond by expressing the most appropriate of its 17 glucose transporters. They do this through a signal transduction pathway that begins at the cell surface with the Snf3 and Rgt2 glucose sensors and ends in the nucleus with the Rgt1 transcription factor that regulates expression of genes encoding glucose transporters. We explain this glucose signal transduction pathway, and describe how it fits into a highly interconnected regulatory network of glucose sensing pathways that probably evolved to ensure rapid and sensitive response of the cell to changing levels of glucose.

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Disruption of pathways regulated by Integrator complex in Galloway–Mowat syndrome due to WDR73 mutations

Scientific Reports ◽

10.1038/s41598-021-84472-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

F. C. Tilley ◽

C. Arrondel ◽

C. Chhuon ◽

M. Boisson ◽

N. Cagnard ◽

...

Keyword(s):

Cell Cycle ◽

Transcription Initiation ◽

Transcriptional Control ◽

Cell Cycle Control ◽

Transcriptional Response ◽

Loss Of Function ◽

Altered Expression ◽

Expression Of Genes ◽

Genes Encoding ◽

Cellular Pathways

AbstractSeveral studies have reported WDR73 mutations to be causative of Galloway–Mowat syndrome, a rare disorder characterised by the association of neurological defects and renal-glomerular disease. In this study, we demonstrate interaction of WDR73 with the INTS9 and INTS11 components of Integrator, a large multiprotein complex with various roles in RNA metabolism and transcriptional control. We implicate WDR73 in two Integrator-regulated cellular pathways; namely, the processing of uridylate-rich small nuclear RNAs (UsnRNA), and mediating the transcriptional response to epidermal growth factor stimulation. We also show that WDR73 suppression leads to altered expression of genes encoding cell cycle regulatory proteins. Altogether, our results suggest that a range of cellular pathways are perturbed by WDR73 loss-of-function, and support the consensus that proper regulation of UsnRNA maturation, transcription initiation and cell cycle control are all critical in maintaining the health of post-mitotic cells such as glomerular podocytes and neurons, and preventing degenerative disease.

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Saccharomyces cerevisiae Engineered for Xylose Metabolism Exhibits a Respiratory Response

Applied and Environmental Microbiology ◽

10.1128/aem.70.11.6816-6825.2004 ◽

2004 ◽

Vol 70 (11) ◽

pp. 6816-6825 ◽

Cited By ~ 105

Author(s):

Yong-Su Jin ◽

Jose M. Laplaza ◽

Thomas W. Jeffries

Keyword(s):

Saccharomyces Cerevisiae ◽

Tricarboxylic Acid Cycle ◽

Pentose Phosphate ◽

Oxygen Limitation ◽

Sugar Uptake ◽

Xylose Utilization ◽

Xylose Metabolism ◽

Expression Of Genes ◽

Genes Encoding ◽

Native Strains

ABSTRACT Native strains of Saccharomyces cerevisiae do not assimilate xylose. S. cerevisiae engineered for d-xylose utilization through the heterologous expression of genes for aldose reductase (XYL1), xylitol dehydrogenase (XYL2), and d-xylulokinase (XYL3 or XKS1) produce only limited amounts of ethanol in xylose medium. In recombinant S. cerevisiae expressing XYL1, XYL2, and XYL3, mRNA transcript levels for glycolytic, fermentative, and pentose phosphate enzymes did not change significantly on glucose or xylose under aeration or oxygen limitation. However, expression of genes encoding the tricarboxylic acid cycle, respiration enzymes (HXK1, ADH2, COX13, NDI1, and NDE1), and regulatory proteins (HAP4 and MTH1) increased significantly when cells were cultivated on xylose, and the genes for respiration were even more elevated under oxygen limitation. These results suggest that recombinant S. cerevisiae does not recognize xylose as a fermentable carbon source and that respiratory proteins are induced in response to cytosolic redox imbalance; however, lower sugar uptake and growth rates on xylose might also induce transcripts for respiration. A petite respiration-deficient mutant (ρÃ¯Â¿Â½) of the engineered strain produced more ethanol and accumulated less xylitol from xylose. It formed characteristic colonies on glucose, but it did not grow on xylose. These results are consistent with the higher respiratory activity of recombinant S. cerevisiae when growing on xylose and with its inability to grow on xylose under anaerobic conditions.

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Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5702-5712.1989 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5702-5712

Author(s):

M Thorsness ◽

W Schafer ◽

L D'Ari ◽

J Rine

Keyword(s):

Saccharomyces Cerevisiae ◽

Enzyme Activity ◽

Transcriptional Control ◽

Coenzyme A ◽

Transcriptional Regulator ◽

Lacz Fusions ◽

Genes Encoding ◽

Yeast Genes ◽

Coenzyme A Reductase

Responses of the yeast genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMG1 and HMG2, to in vivo changes in heme concentrations were investigated. Expression of the genes was determined by direct measurement of the mRNA transcribed from each gene, by direct assay of the enzyme activity encoded by each gene, and by measurement of the expression of lacZ fusions to the control regions of each gene. These studies indicated that expression of HMG1 was stimulated by heme, whereas expression of HMG2 was repressed by heme. The effect of heme on HMG1 expression was mediated by the HAP1 transcriptional regulator and was independent of HAP2. Thus, the genes encoding the 3-hydroxy-3-methylglutaryl coenzyme A reductase isozymes join a growing list of gene pairs that are regulated by heme in opposite ways.

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The DYRK1A protein kinase regulates ribosome mass and translation rates through transcriptional control of ribosomal protein genes expression

10.1101/2021.01.21.427583 ◽

2021 ◽

Author(s):

Chiara Di Vona ◽

Laura Barba ◽

Roberto Ferrari ◽

Susana de la Luna

Keyword(s):

Ribosomal Proteins ◽

Transcriptional Control ◽

Protein Translation ◽

Ribosomal Protein Genes ◽

Expression Of Genes ◽

Specific Subset ◽

Cell Proliferation And Differentiation ◽

Dual Specificity ◽

Global Protein Synthesis ◽

Genes Encoding

ABSTRACTRibosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated, both to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes (RPGs) have been characterized in yeast and Drosophila, yet how cells regulate the production of RPs in mammals is less well understood. The dual-specificity tyrosine-regulated kinase 1A (DYRK1A) is known to participate in cell proliferation and differentiation in mammals, and its dysregulation is associated with disease in humans. Here, we show that DYRK1A marks a specific subset of proximal RPG promoters, which are characterized by the presence of the palindromic TCTCGCGAGA motif. The presence of DYRK1A at these promoters is associated with enhanced binding of the TATA-binding protein, TBP, and it is negatively correlated with the binding of the GABP transcription factor, establishing at least two clusters of RPGs that could be coordinately regulated. Indeed, DYRK1A depletion leads to a reduction of both RP mRNA and protein. Significantly, cells in which DYRK1A is depleted have fewer ribosomes, reduced global protein synthesis and they are smaller. Based on these results, we propose a novel role for DYRK1A in coordinating the expression of genes encoding RPs, thereby controlling cell growth in mammals.

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Transcriptional and Post-transcriptional Control of the Nitrate Respiration in Bacteria

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.667758 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sylvain Durand ◽

Maude Guillier

Keyword(s):

Metabolic Pathways ◽

Transcriptional Control ◽

Reduction Potential ◽

Anaerobic Respiration ◽

Aerobic Bacteria ◽

Nitrate Respiration ◽

Expression Of Genes ◽

Genes Encoding ◽

Small Regulatory Rnas ◽

Regulatory Rnas

In oxygen (O2) limiting environments, numerous aerobic bacteria have the ability to shift from aerobic to anaerobic respiration to release energy. This process requires alternative electron acceptor to replace O2 such as nitrate (NO3–), which has the next best reduction potential after O2. Depending on the organism, nitrate respiration involves different enzymes to convert NO3– to ammonium (NH4+) or dinitrogen (N2). The expression of these enzymes is tightly controlled by transcription factors (TFs). More recently, bacterial small regulatory RNAs (sRNAs), which are important regulators of the rapid adaptation of microorganisms to extremely diverse environments, have also been shown to control the expression of genes encoding enzymes or TFs related to nitrate respiration. In turn, these TFs control the synthesis of multiple sRNAs. These results suggest that sRNAs play a central role in the control of these metabolic pathways. Here we review the complex interplay between the transcriptional and the post-transcriptional regulators to efficiently control the respiration on nitrate.

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Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.9.12.5702 ◽

1989 ◽

Vol 9 (12) ◽

pp. 5702-5712 ◽

Cited By ~ 57

Author(s):

M Thorsness ◽

W Schafer ◽

L D'Ari ◽

J Rine

Keyword(s):

Saccharomyces Cerevisiae ◽

Enzyme Activity ◽

Transcriptional Control ◽

Coenzyme A ◽

Transcriptional Regulator ◽

Lacz Fusions ◽

Genes Encoding ◽

Yeast Genes ◽

Coenzyme A Reductase

Responses of the yeast genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, HMG1 and HMG2, to in vivo changes in heme concentrations were investigated. Expression of the genes was determined by direct measurement of the mRNA transcribed from each gene, by direct assay of the enzyme activity encoded by each gene, and by measurement of the expression of lacZ fusions to the control regions of each gene. These studies indicated that expression of HMG1 was stimulated by heme, whereas expression of HMG2 was repressed by heme. The effect of heme on HMG1 expression was mediated by the HAP1 transcriptional regulator and was independent of HAP2. Thus, the genes encoding the 3-hydroxy-3-methylglutaryl coenzyme A reductase isozymes join a growing list of gene pairs that are regulated by heme in opposite ways.

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