Global expression profiling of yeast treated with an inhibitor of amino acid biosynthesis, sulfometuron methyl

Jia, Melissa H.; LaRossa, Robert A.; Lee, Jian-Ming; Rafalski, Antoni; Derose, Ellen J.; Gonye, Greg; Xue, Zhixiong

doi:10.1152/physiolgenomics.2000.3.2.83

Cited by 121 publications

(115 citation statements)

References 53 publications

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“…6). SMM is a specific inhibitor of acetolactate synthase, which causes a depletion of branched-chain amino acids in the cell (Jia et al 2000). Surprisingly, the nab4 mutants showed a growth advantage in comparison to wild-type cells when exposed to SMM.…”

Section: Growth Phenotype Correlates With Association In the Rna-ip Mmentioning

confidence: 99%

Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA binding profiles

Guisbert

Duncan²,

Li³

et al. 2005

RNA

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Nab2, Npl3, and Nab4/Hrp1 are essential RNA binding proteins of the shuttling hnRNP class that are required for the efficient export of mRNA. To characterize the in vivo transcript specificity of these proteins, we identified their mRNA binding partners using a microarray-based assay. Each of the three proteins was coimmunoprecipitated with many different mRNA transcripts. Interestingly, each protein exhibits preferential associations with a distinct set of mRNAs. Notably, some of these appear to denote specific functional classes. For example, the ribosomal protein mRNAs and other highly expressed transcripts significantly favor association with Npl3 over Nab2, and Nab4/Hrp1 is strongly enriched with transcripts required for amino acid metabolism. Significantly, nab4 mutants showed a striking, desensitized growth phenotype when exposed to amino acid stress conditions suggesting a biological consequence to the associations we observed. Supporting the hypothesis that these proteins display transcript specificity, we identified a unique 7-nucleotide sequence overrepresented in the transcripts highly associated with Nab2 and Nab4/Hrp1 using the REDUCE algorithm. Validating our approach, our bioinformatics analysis correctly identified the known binding site for Nab4/Hrp1. These specialized associations of the hnRNP proteins of Saccharomyces cerevisiae suggest the opportunity to regulate the processing of particular transcripts between transcription and translation.

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Section: Growth Phenotype Correlates With Association In the Rna-ip Mmentioning

confidence: 99%

Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA binding profiles

Guisbert

Duncan²,

Li³

et al. 2005

RNA

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show abstract

“…Furthermore, in the absence of any amino acid deficiency, a basal level of Gcn4 mRNA translation is required for the transcription of several genes (e.g., HIS3, ARG4, ARG3, and ARO3) (57). Two genomic studies have aimed to identify the whole set of GAAC target genes (68,90). In one of them (90), 539 genes whose expression is activated in a Gcn4-dependent manner in amino acid-starved cells were listed.…”

mentioning

confidence: 99%

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Godard

Urrestarazu

Vissers

et al. 2007

Molecular and Cellular Biology

217

270

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We compared the transcriptomes of Saccharomyces cerevisiae cells growing under steady-state conditions on 21 unique sources of nitrogen. We found 506 genes differentially regulated by nitrogen and estimated the activation degrees of all identified nitrogen-responding transcriptional controls according to the nitrogen source. One main group of nitrogenous compounds supports fast growth and a highly active nitrogen catabolite repression (NCR) control. Catabolism of these compounds typically yields carbon derivatives directly assimilable by a cell's metabolism. Another group of nitrogen compounds supports slower growth, is associated with excretion by cells of nonmetabolizable carbon compounds such as fusel oils, and is characterized by activation of the general control of amino acid biosynthesis (GAAC). Furthermore, NCR and GAAC appear interlinked, since expression of the GCN4 gene encoding the transcription factor that mediates GAAC is subject to NCR. We also observed that several transcriptional-regulation systems are active under a wider range of nitrogen supply conditions than anticipated. Other transcriptional-regulation systems acting on genes not involved in nitrogen metabolism, e.g., the pleiotropic-drug resistance and the unfolded-protein response systems, also respond to nitrogen. We have completed the lists of target genes of several nitrogen-sensitive regulons and have used sequence comparison tools to propose functions for about 20 orphan genes. Similar studies conducted for other nutrients should provide a more complete view of alternative metabolic pathways in yeast and contribute to the attribution of functions to many other orphan genes.

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“…This system mediates increased transcription of more than 500 genes in response to starvation for an amino acid (2)(3)(4). The induced genes encode amino acid and purine biosynthetic enzymes and a variety of proteins involved peripherally in amino acid biosynthesis or in amino acid uptake or salvage (autophagy) (4,5).…”

mentioning

confidence: 99%

Serine 577 Is Phosphorylated and Negatively Affects the tRNA Binding and eIF2α Kinase Activities of GCN2

Garcia-Barrio

Dong

Cherkasova

et al. 2002

Journal of Biological Chemistry

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Protein kinase GCN2 regulates translation initiation by phosphorylating eukaryotic initiation factor 2␣ (eIF2␣), impeding general protein synthesis but specifically inducing translation of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCN2 activity is stimulated in amino acid-deprived cells through binding of uncharged tRNA to a domain related to histidyl tRNA synthetase. We show that GCN2 is phosphorylated by another kinase on serine 577, located N-terminal to the kinase domain. Mutation of Ser-577 to alanine produced partial activation of GCN2 in nonstarved cells, increasing the level of phosphorylated eIF2␣, derepressing GCN4 expression, and elevating the cellular levels of tryptophan and histidine. The Ala-577 mutation also increased the tRNA binding affinity of purified GCN2, which can account for the elevated kinase activity of GCN2-S577A in nonstarved cells where uncharged tRNA levels are low. Whereas Ser-577 remains phosphorylated in amino acidstarved cells, its dephosphorylation could mediate GCN2 activation in other stress or starvation conditions by lowering the threshold of uncharged tRNA required to activate the protein.

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Global expression profiling of yeast treated with an inhibitor of amino acid biosynthesis, sulfometuron methyl

Cited by 121 publications

References 53 publications

Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA binding profiles

Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA binding profiles

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Serine 577 Is Phosphorylated and Negatively Affects the tRNA Binding and eIF2α Kinase Activities of GCN2

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