The glucose repression and RAS-cAMP signal transduction pathways of Saccharomyces cerevisiae each affect RNA processing and the synthesis of a reporter protein

ABSTRACT The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.

Download Full-text

Coordination of RNA Processing Regulation by Signal Transduction Pathways

Biomolecules ◽

10.3390/biom11101475 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1475

Author(s):

Veronica Ruta ◽

Vittoria Pagliarini ◽

Claudio Sette

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Rna Processing ◽

Translational Regulation ◽

Rna Binding ◽

Rna Binding Proteins ◽

Regulation Of Gene Expression ◽

Signal Transduction Pathways ◽

Challenges And Opportunities ◽

Common Signal

Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.

Download Full-text

The Saccharomyces cerevisiae RanGTP-Binding Protein Msn5p Is Involved in Different Signal Transduction Pathways

Genetics ◽

10.1093/genetics/153.3.1219 ◽

1999 ◽

Vol 153 (3) ◽

pp. 1219-1231

Author(s):

Paula M Alepuz ◽

Dina Matheos ◽

Kyle W Cunningham ◽

Francisco Estruch

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Signal Transduction Pathway ◽

Small Gtpase ◽

Signal Transduction Pathways ◽

Phenotypic Analysis ◽

Yeast Saccharomyces Cerevisiae ◽

Extracellular Signals ◽

External Conditions ◽

Gtpase Ran

Abstract In eukaryotes, control of transcription by extracellular signals involves the translocation to the nucleus of at least one component of the signal transduction pathway. Transport through the nuclear envelope requires the activity of an import or export receptor that interacts with the small GTPase Ran. We have cloned the MSN5 gene of the yeast Saccharomyces cerevisiae that is postulated to encode one of these receptors. Msn5p belongs to a family of proteins with a conserved N-terminal sequence that acts as a RanGTP-binding domain. The results presented here provide genetic data supporting Msn5p involvement in several different signal transduction pathways. All of these pathways include changes in gene expression, and regulated nucleocytoplasmic redistribution of a component in response to external conditions has already been described in some of them. We have cloned MSN5 following two different strategies. Msn5p was constitutively localized in the nucleus. Phenotypic analysis of the msn5 mutant demonstrated that this protein participates in processes such as catabolite repression, calcium signaling, mating, and cell proliferation, as well as being involved in previously characterized phosphate utilization. Therefore, Msn5p could be a receptor for several proteins involved in different signaling pathways.

Download Full-text

Yeast MEK-dependent signal transduction: response thresholds and parameters affecting fidelity.

Molecular and Cellular Biology ◽

10.1128/mcb.15.12.6545 ◽

1995 ◽

Vol 15 (12) ◽

pp. 6545-6553 ◽

Cited By ~ 45

Author(s):

B Yashar ◽

K Irie ◽

J A Printen ◽

B J Stevenson ◽

G F Sprague ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Signal Transduction Pathways ◽

Cell Integrity ◽

Genetic Screens ◽

Dependent Signal ◽

Response Thresholds ◽

Inductive Signal ◽

Full Activation ◽

Erk Kinase

Ste7p and Mkk1p are MEK (MAPK/ERK kinase) family members that function in the mating and cell integrity signal transduction pathways in Saccharomyces cerevisiae. We selected STE7 and MKK1 mutations that stimulated their respective pathways in the absence of an inductive signal. Strikingly, serine-to-proline substitutions at analogous positions in Ste7p (position 368) and Mkk1p (position 386) were recovered by independent genetic screens. Such an outcome suggests that this substitution in other MEKs would exhibit similar properties. The Ste7p-P368 variant has higher basal enzymatic activity than Ste7p but still requires induction to reach full activation. The higher activity associated with Ste7p-P368 allows it to compensate for defects in the cell integrity pathway, but it does so only when it is overproduced or when Ste5p is missing. This behavior suggests that Ste5p, which has been proposed to be a tether for the kinases in the mating pathway, contributes to Ste7p specificity.

Download Full-text

A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6.

Molecular Biology of the Cell ◽

10.1091/mbc.7.12.1953 ◽

1996 ◽

Vol 7 (12) ◽

pp. 1953-1966 ◽

Cited By ~ 89

Author(s):

H Liang ◽

R F Gaber

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Glucose Uptake ◽

Glucose Repression ◽

Carbon Sources ◽

Signal Transduction Pathway ◽

Transduction Pathway ◽

Signaling Mechanism ◽

High Concentrations ◽

Delta Cells

We show that cells deleted for SNF3, HXT1, HXT2, HXT3, HXT4, HXT6, and HXT7 do not take up glucose and cannot grow on media containing glucose as a sole carbon source. The expression of Hxt1, Hxt2, Hxt3, Hxt6, or Gal2 in these cells resulted in glucose transport and allowed growth on glucose media. In contrast, the expression of Snf3 failed to confer glucose uptake or growth on glucose. HXT6 is highly expressed on raffinose, low glucose, or nonfermentable carbon sources but is repressed in the presence of high concentrations of glucose. The maintenance of HXT6 glucose repression is strictly dependent on Snf3 and not on intracellular glucose. In snf3 delta cells expression of HXT6 is constitutive even when the entire repertoire of HXT genes is present and glucose uptake is abundant. In addition, glucose repression of HXT6 does not require glucose uptake by HXT1, HXT2, HXT3 or HXT4. We show that a signal transduction pathway defined by the Snf3-dependent hexose regulation of HXT6 is distinct from but also overlaps with general glucose regulation pathways in Saccharomyces cerevisiae. Finally, glucose repression of ADH2 and SUC2 is intact in snf3 delta hxt1 delta hxt2 delta hxt3 delta hxt4 delta hxt6 delta hxt7 delta gal2 cells, suggesting that the sensing and signaling mechanism for general glucose repression is independent from glucose uptake.

Download Full-text

Sensing, Uptake and Catabolism of L-Phenylalanine During 2-Phenylethanol Biosynthesis via the Ehrlich Pathway in Saccharomyces cerevisiae

Frontiers in Microbiology ◽

10.3389/fmicb.2021.601963 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jun Dai ◽

Huili Xia ◽

Chunlei Yang ◽

Xiong Chen

Keyword(s):

Saccharomyces Cerevisiae ◽

Signal Transduction ◽

Chemical Synthesis ◽

Future Research ◽

Signal Transduction Pathways ◽

Ehrlich Pathway ◽

Research Directions ◽

Future Research Directions

2-Phenylethanol (2-PE) is an important flavouring ingredient with a persistent rose-like odour, and it has been widely utilized in food, perfume, beverages, and medicine. Due to the potential existence of toxic byproducts in 2-PE resulting from chemical synthesis, the demand for “natural” 2-PE through biotransformation is increasing. L-Phenylalanine (L-Phe) is used as the precursor for the biosynthesis of 2-PE through the Ehrlich pathway by Saccharomyces cerevisiae. The regulation of L-Phe metabolism in S. cerevisiae is complicated and elaborate. We reviewed current progress on the signal transduction pathways of L-Phe sensing, uptake of extracellular L-Phe and 2-PE synthesis from L-Phe through the Ehrlich pathway. Moreover, the anticipated bottlenecks and future research directions for S. cerevisiae biosynthesis of 2-PE are discussed.

Download Full-text

Signal-regulated oxidation of proteins via MICAL

Biochemical Society Transactions ◽

10.1042/bst20190866 ◽

2020 ◽

Vol 48 (2) ◽

pp. 613-620

Author(s):

Clara Ortegón Salas ◽

Katharina Schneider ◽

Christopher Horst Lillig ◽

Manuela Gellert

Keyword(s):

Signal Transduction ◽

Hydrogen Peroxide ◽

Cell Death ◽

Redox Regulation ◽

Signal Transduction Pathways ◽

Cellular Functions ◽

Intracellular Signals ◽

Amino Acid Side Chains ◽

Specific Receptors ◽

Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

Download Full-text