Cellular adaptation to amino acid availability: mechanisms involved in the regulation of gene expression.

The impact of nutrients on gene expression in mammals has become an important area of research. Nevertheless, the current understanding of the amino acid-dependent control of gene expression is limited. Because amino acids have multiple and important functions, their homoeostasis has to be finely maintained. However, amino-acidaemia can be affected by certain nutritional conditions or various forms of stress. It follows that mammals have to adjust several of their physiological functions involved in the adaptation to amino acid availability by regulating the expression of numerous genes. The aim of the present review is to examine the role of amino acids in regulating mammalian gene expression and protein turnover. It has been reported that some genes involved in the control of growth or amino acid metabolism are regulated by amino acid availability. For instance, limitation of several amino acids greatly increases the expression of the genes encoding insulin-like growth factor binding protein-1, CHOP (C/EBP homologous protein, where C/EBP is CCAAT/enhancer binding protein) and asparagine synthetase. Elevated mRNA levels result from both an increase in the rate of transcription and an increase in mRNA stability. Several observations suggest that the amino acid regulation of gene expression observed in mammalian cells and the general control process described in yeast share common features. Moreover, amino acid response elements have been characterized in the promoters of the CHOP and asparagine synthetase genes. Taken together, the results discussed in the present review demonstrate that amino acids, by themselves, can, in concert with hormones, play an important role in the control of gene expression.

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Transcriptional and Translational Regulation of Gene Expression in the General Control of Amino-Acid Biosynthesis in Saccharomyces cerevisiae

Progress in Nucleic Acid Research and Molecular Biology ◽

10.1016/s0079-6603(08)60712-6 ◽

1990 ◽

pp. 195-240 ◽

Cited By ~ 33

Author(s):

Alan G. Hinnebusch

Keyword(s):

Gene Expression ◽

Saccharomyces Cerevisiae ◽

Amino Acid ◽

Translational Regulation ◽

Regulation Of Gene Expression ◽

Amino Acid Biosynthesis ◽

General Control ◽

Acid Biosynthesis ◽

Transcriptional And Translational Regulation

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Transcriptome and Proteome Analysis of Bacillus subtilis Gene Expression Modulated by Amino Acid Availability

Journal of Bacteriology ◽

10.1128/jb.184.15.4288-4295.2002 ◽

2002 ◽

Vol 184 (15) ◽

pp. 4288-4295 ◽

Cited By ~ 45

Author(s):

Ulrike Mäder ◽

Georg Homuth ◽

Christian Scharf ◽

Knut Büttner ◽

Rüdiger Bode ◽

...

Keyword(s):

Gene Expression ◽

Bacillus Subtilis ◽

Amino Acid ◽

Expression Patterns ◽

Proteome Analysis ◽

Protein Gel ◽

Amino Acid Availability ◽

Physiological Relevance ◽

Casamino Acids

ABSTRACT A comprehensive study of Bacillus subtilis gene expression patterns in response to amino acid availability was performed by means of proteomics and transcriptomics. The methods of two-dimensional protein gel electrophoresis and DNA macroarray technology were combined to analyze cells exponentially grown in minimal medium with and without 0.2% Casamino Acids (CAA). This approach revealed about 120 genes predominantly involved in amino acid biosynthesis, sporulation, and competence, which were downregulated in CAA-containing medium. Determination of sporulation frequencies confirmed the physiological relevance of the expression data.

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Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity

International Journal of Molecular Sciences ◽

10.3390/ijms20061386 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1386 ◽

Cited By ~ 6

Author(s):

Diego Haro ◽

Pedro Marrero ◽

Joana Relat

Keyword(s):

Gene Expression ◽

Amino Acid ◽

Molecular Mechanisms ◽

Metabolic Diseases ◽

Regulation Of Gene Expression ◽

Peroxisome Proliferator ◽

Nutritional Regulation ◽

Control Of Gene Expression ◽

Nutritional Interventions ◽

Precise Control

The ability to detect changes in nutrient levels and generate an adequate response to these changes is essential for the proper functioning of living organisms. Adaptation to the high degree of variability in nutrient intake requires precise control of metabolic pathways. Mammals have developed different mechanisms to detect the abundance of nutrients such as sugars, lipids and amino acids and provide an integrated response. These mechanisms include the control of gene expression (from transcription to translation). This review reports the main molecular mechanisms that connect nutrients’ levels, gene expression and metabolism in health. The manuscript is focused on sugars’ signaling through the carbohydrate-responsive element binding protein (ChREBP), the role of peroxisome proliferator-activated receptors (PPARs) in the response to fat and GCN2/activating transcription factor 4 (ATF4) and mTORC1 pathways that sense amino acid concentrations. Frequently, alterations in these pathways underlie the onset of several metabolic pathologies such as obesity, insulin resistance, type 2 diabetes, cardiovascular diseases or cancer. In this context, the complete understanding of these mechanisms may improve our knowledge of metabolic diseases and may offer new therapeutic approaches based on nutritional interventions and individual genetic makeup.

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Amino acid limitation regulates gene expression

Proceedings of The Nutrition Society ◽

10.1017/s0029665199000828 ◽

1999 ◽

Vol 58 (3) ◽

pp. 625-632 ◽

Cited By ~ 29

Author(s):

Alain Bruhat ◽

Céline Jousse ◽

Pierre Fafournoux

Keyword(s):

Gene Expression ◽

Amino Acids ◽

Amino Acid ◽

Molecular Mechanisms ◽

Binding Protein ◽

Regulation Of Gene Expression ◽

Essential Amino Acids ◽

Mrna Levels ◽

Dependent Manner ◽

Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

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