Biomedical subjects

Claude Jacq

Publications and source records attributed to Claude Jacq.

10 recordsLinked to original sources

PubMed2003

Ssu72 is a phosphatase essential for transcription termination of snoRNAs and specific mRNAs in yeast.

Ssu72 is an essential yeast protein that is involved in transcription. It physically interacts with transcription initiation and termination complexes. In this report, we provide evidence that Ssu72 is a phosphatase that physically interacts with the CTD kinase Kin28 and functionally interacts with the CTD phosphatase Fcp1. A genome-wide expression analysis of mutant ssu72-ts69 during growth in complete medium revealed a number of defects, including the accumulation of a limited number of mRNAs and the read-through transcription of small nucleolar RNAs and of some mRNAs. We hypothesize that Ssu72 plays a key role in the transcription termination of certain transcripts, possibly by promoting RNA polymerase pausing and release. The possibility that the CTD of the largest subunit of RNA polymerase II is a substrate of Ssu72 is discussed.

Amino Acid Sequence↗

PubMed2003

A general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast.

We demonstrate a genomewide approach to determine the physiological role of a putative transcription factor, Ylr266, identified through yeast genome sequencing program. We constructed activated forms of the zinc finger (Zn(2)Cys(6)) protein Ylr266, and we analyzed the corresponding transcriptomes with DNA microarrays to characterize the up-regulated genes. The direct target genes of Ylr266 were further identified by in vivo chromatin immunoprecipitation procedure. The functions of the genes directly controlled by YLR266c are in agreement with the observed drug-resistance phenotype of the cell expressing an activated form of Ylr266. These target genes code for ATP-binding cassette or major facilitator superfamily transporters such as PDR15, YOR1, or AZR1 or for other proteins such as SNG1, YJL216c, or YLL056c which are already known to be involved in the yeast pleiotropic drug resistance (PDR) phenomenon. YLR266c could thus be named PDR8. Overlaps with the other PDR networks argue in favor of a new specific role for PDR8 in connection with the well known PDR regulators PDR1/PDR3 and YRR1. This strategy to identify the regulatory properties of an anonymous transcription factor is likely to be generalized to all the Zn(2)Cys(6) transcription factors from Saccharomyces cerevisiae and related yeasts.

Drug Resistance, Microbial↗

PubMed2003

Domestication of wild Saccharomyces cerevisiae is accompanied by changes in gene expression and colony morphology.

Although colonies from Saccharomyces cerevisiae laboratory strains are smooth, those isolated from nature exhibit a structured fluffy pattern. Environmental scanning electron microscopy shows that the cells within wild fluffy colonies are connected by extracellular matrix (ECM) material. This material contains a protein of about 200 kDa unrelated to the flocculins, proteins involved in cell-cell adhesion in liquid media. The matrix material binds to concanavalin A. Within a few passages on rich agar medium, the wild strains switch from the fluffy to the smooth colony morphology. This domestication is accompanied by loss of the ECM and by extensive changes in gene expression as detected by DNA microarrays. The expression of about 320 genes was changed in smooth colonies. The major changes comprise carbohydrate metabolism, cell wall, water channels, Ty-transposons and subtelomeric genes, iron homeostasis, vitamin metabolism and cell cycle and polarity. The growth in fluffy colonies may represent a metabolic strategy for survival of yeast under unfavourable conditions that is switched off under felicitous laboratory conditions.

Computational Biology↗

PubMed2002

In Saccharomyces cerevisiae, ATP2 mRNA sorting to the vicinity of mitochondria is essential for respiratory function.

We recently demonstrated that polysome-associated mRNAs that co-isolate with mitochondria encode a subset of mitochondrial proteins, and that the 3' UTRs of these transcripts are essential for their localization to the vicinity of the organelle. To address the question of the involvement of the mRNA targeting process in mitochondrial biogenesis, we studied the role of ATP2 3' UTR. An altered ATP2 allele in which the 3' UTR was replaced by the ADH1 3' UTR exhibits properties supporting the importance of mRNA localization to the vicinity of mitochondria: (i) the mutated strain presents a respiratory dysfunction; (ii) mitochondrial import of the protein translated from the altered gene is strongly reduced, even though the precursor is addressed to the organelle surface; (iii) systematic deletions of ATP2 3' UTR revealed a 100 nucleotide element presenting RNA targeting properties. Additionally, when the ATM1 3' UTR was replaced by the ADH1 3' UTR, we obtained cells in which ATM1 mRNA is also delocalized, and presenting a respiratory dysfunction. This demonstrates that mRNA localization to the vicinity of mitochondria plays a critical role in organelle biogenesis.

3' Untranslated Regions↗

PubMed2002

Genome-wide studies on the nuclear PDR3-controlled response to mitochondrial dysfunction in yeast.

Gain-of-function mutations in the transcription factors Pdr1p and Pdr3p lead to the up-regulation of genes controlling plasma membrane properties. Pdr3p is involved in a retrograde response in which mitochondrial dysfunctions activate PDR5, a gene encoding an ABC membrane transporter. We carried out genome-wide analyses of the PDR3-controlled genes activated by the deletion of the mitochondrial DNA. We present evidence showing that PDR1 does not interfere with this PDR3 response. We also showed that the mitochondrially activated PDR3 response is highly sensitive to both yeast strain variations and carbon sources. These observations explain the apparent discrepancies in published studies and better describe the connections between the mitochondrial state and plasma membrane properties.

ATP-Binding Cassette Transporters↗

PubMed2002

Genome-wide analysis of mRNAs targeted to yeast mitochondria.

It is agreed that nuclear-encoded mitochondrial proteins are post-translationally targeted to mitochondria, even if, in some cases, a co-translational phase can assist the import of precursor proteins. We used yeast DNA microarrays to analyse the mRNA populations associated with free and mitochondrion-bound polysomes. As expected, many mRNAs, known to encode mitochondrial proteins, are localized to free cytoplasmic polysomes, but many are localized to mitochondrion-bound polysomes. Furthermore, the 3'-UTR of six randomly chosen mitochondrion-bound mRNAs contains sufficient information to target, in vivo, non-translatable RNA to the vicinity of mitochondria. Interestingly, genes producing mRNAs that are targeted to mitochondria are mainly of ancient bacterial origin, whereas those producing mRNAs that are translated in the cytoplasm are mainly of eukaryotic origin. These observations, which support the recent hypotheses concerning the dual origin of the mitochondrial proteome, provide new insights into the biogenesis of mitochondria.

DNA, Mitochondrial↗

PubMed2002

yMGV: helping biologists with yeast microarray data mining.

yMGV (yeast Microarray Global Viewer) was designed to provide biologists with meaningful information from genome-wide yeast expression data. The database includes most of the available expression data published on yeast microarrays over the last 4 years. It provides customizable tools for the rapid visualization of expression profiles associated with a set of genes from all published experiments. It also allows users to compare the results from different publications so that they can identify genes with common expression profiles. We used yMGV to perform global analyses to find a gene expression profile specific for given biological conditions and to locate functional gene clusters on chromosomes. Other organisms will be added to this database. yMGV is accessible on the web at http://transcriptome.ens.fr/ymgv.

Computer Graphics↗

PubMed2002

Ammonia pulses and metabolic oscillations guide yeast colony development.

On solid substrate, growing yeast colonies alternately acidify and alkalinize the medium. Using morphological, cytochemical, genetic, and DNA microarray approaches, we characterized six temporal steps in the "acid-to-alkali" colony transition. This transition is connected with the production of volatile ammonia acting as starvation signal between colonies. We present evidence that the three membrane proteins Ato1p, Ato2p, and Ato3p, members of the YaaH family, are involved in ammonia production in Saccharomyces cerevisiae colonies. The acid-to-alkali transition is connected with decrease of mitochondrial oxidative catabolism and by peroxisome activation, which in parallel with activation of biosynthetic pathways contribute to decrease the general stress level in colonies. These metabolic features characterize a novel survival strategy used by yeast under starvation conditions prevalent in nature.

Amino Acid Sequence↗

PubMed2002

Arrayplot for visualization and normalization of cDNA microarray data.

UNLABELLED: Arrayplot is an application which allows filtering, visualization and normalization of raw cDNA microarray data. AVAILABILITY: MS-Windows binaries are freely available for non-profit use at http://www.biologie.ens.fr/yeast-publi.html. SUPPLEMENTARY INFORMATION: Scripts for online creation of Arrayplot files are available at http://transcriptome.ens.fr/lgm_bioinfo/

Computational Biology↗

PubMed2002

New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system.

Yrr1p is a recently described Zn(2)Cys(6) transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

Amino Acid Sequence↗