Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression analysis of yeast strains with a nonsense mutation in the eRF3-coding gene highlights possible mechanisms of adaptation

ABSTRACT: In yeast Saccharomyces cerevisiae, there are two translation termination factors, eRF1 (SUP45) and eRF3 (SUP35), which are essential for viability. Previous studies have revealed that presence of nonsense mutations in these genes leads to amplification of mutant alleles (sup35-n and sup45-n) which appears to be necessary for viability of such cells. However, the mechanism of this phenomenon remained unclear. In this study, we used RNA-Seq to reveal the complete set of gene expression changes that occur during cellular adaptation to the introduction of the sup35-218 nonsense allele. Our analysis demonstrated significant changes in the transcription of genes that control the cell cycle: decrease in the expression of genes of the anaphase promoting complex APC/C (APC9, CDC23), their activator CDC20 and an increase in the expression of FKH1 transcription factor, main cell cycle kinase CDC28 and cyclins that induce DNA biosynthesis. We propose a model according to which yeast adaptation to nonsense mutations in the translation termination factor genes occurs as a result of a delayed cell cycle progression beyond the G2-M stage, which leads to an extension of the S and G2 phases and an increase in the number of copies of the mutant sup35-n allele.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE267888 | GEO | 2024/05/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Divergent effects of eRF3 and Upf1 on the expression of uORF carrying mRNAs and ribosome protein genes

Project description:In addition to its role in translation termination, eRF3 has been implicated in the nonsense-mediated mRNA decay (NMD) pathway through its interaction with Upf1. NMD is a RNA quality control mechanism, which detects and degrades aberrant mRNAs as well as some normal transcripts including those that harbor upstream open reading frames in their 5' leader sequence and long 3′ UTR. In this study, we used RNA-sequencing and ribosome profiling to perform a genome wide analysis of the effect of either eRF3 or Upf1 depletion in human cells. Our bioinformatics analyses allow to delineate the features of the transcripts controlled by eRF3 and Upf1 and to compare the effect of each of these factors on gene expression. We show that eRF3 and Upf1 have very different impact on the human transcriptome, only ~250 transcripts being targeted by both factors. We also show that in contrast to Upf1, eRF3a depletion globally derepressed the expression of mRNAs containing translated uORFs. Finally, we find that eRF3a and Upf1 have opposite effects on ribosome protein gene expression. Together, our results provide important elements for understanding the impact of translation termination and NMD on the human transcriptome and reveal novel determinants of ribosome biogenesis regulation.

2019-10-27 | GSE126385 | GEO

Fkh1 and Fkh2 Bind Multiple Chromosomal Elements in the S. cerevisiae Genome with Distinct Specificities and Cell Cycle Dynamics

Project description:Forkhead box (FOX) transcription factors regulate a wide variety of cellular functions in higher eukaryotes, including cell cycle control and developmental regulation. In Saccharomyces cerevisiae, Forkhead proteins Fkh1 and Fkh2 perform analogous functions, regulating genes involved in cell cycle control, while also regulating matingtype silencing and switching involved in gamete development. Recently, we revealed a novel role for Fkh1 and Fkh2 in the regulation of replication origin initiation timing, which, like donor preference in mating-type switching, appears to involve long-range chromosomal interactions, suggesting roles for Fkh1 and Fkh2 in chromatin architecture and organization. To elucidate how Fkh1 and Fkh2 regulate their target DNA elements and potentially regulate the spatial organization of the genome, we undertook a genome-wide analysis of Fkh1 and Fkh2 chromatin binding by ChIP-chip using tiling DNA microarrays. Our results confirm and extend previous findings showing that Fkh1 and Fkh2 control the expression of cell cycle-regulated genes. In addition, the data reveal hundreds of novel loci that bind Fkh1 only and exhibit a distinct chromatin structure from loci that bind both Fkh1 and Fkh2. The findings also show that Fkh1 plays the predominant role in the regulation of a subset of replication origins that initiate replication early, and that Fkh1/2 binding to these loci is cell cycleregulated. Finally, we demonstrate that Fkh1 and Fkh2 bind proximally to a variety of genetic elements, including centromeres and Pol III-transcribed snoRNAs and tRNAs, greatly expanding their potential repertoire of functional targets, consistent with their recently suggested role in mediating the spatial organization of the genome.

2014-02-05 | GSE52467 | GEO

Fkh1 and Fkh2 Bind Multiple Chromosomal Elements in the S. cerevisiae Genome with Distinct Specificities and Cell Cycle Dynamics

2014-02-05 | E-GEOD-52467 | biostudies-arrayexpress

Cell cycle gene expression control

Project description:Gene expression data for cdc28-13 yeast released synchronously into the cell cycle.

2015-05-01 | GSE13232 | GEO

Control of Cdc28 CDK1 by a stress-induced lncRNA

Project description:Genomic analysis has revealed the existence of a large number of long non-coding RNAs (lncRNAs) in a variety of organisms, including yeast. lncRNAs might have several biological functions during normal cell growth and development. Cells are subject to dramatic changes of gene expression in response to environmental changes. Using whole-genome tiling arrays, we found that a set of lncRNAs are induced specifically by the Hog1 stress-activated protein kinase (SAPK) in response to stress. Cdc28 kinase controls the cell cycle in yeast and there is a stress-induced lncRNA in the antisense orientation in CDC28, which permits Hog1 and RSC to induce CDC28 gene expression by remodeling the +1 nucleosome. Increased levels of Cdc28 mediate a more efficient cell cycle re-entry after stress. Therefore, Hog1 mediates changes on the level of Cdc28 protein by induction of a specific lncRNA.

2014-02-18 | E-MTAB-1686 | biostudies-arrayexpress

Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates Candida albicans pathogenesis.

Project description:The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. Transcript profiling of Fkh2 deletion and non-phosphrylatable mutants in yeast and hypae revealed that the the hyphal-specific shift in the phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes

2015-03-11 | GSE64383 | GEO

Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth

Project description:There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell-cycle regulated. Some of these form clusters of co-regulated genes. The 'CLB2' cluster contains 33 genes whose transcription peaks early in mitosis, including CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis. Here we find that the genes in this cluster lose their cell cycle regulation in a mutant that lacks two forkhead transcription factors, Fkh1 and Fkh2. Fkh2 protein is associated with the promoters of CLB2, SWI5 and other genes of the cluster. These results indicate that Fkh proteins are transcription factors for the CLB2 cluster. The fkh1 fkh2 mutant also displays aberrant regulation of the 'SIC1' cluster, whose member genes are expressed in the M-G1 interval and are involved in mitotic exit. This aberrant regulation may be due to aberrant expression of the transcription factors Swi5 and Ace2, which are members of the CLB2 cluster and controllers of the SIC1 cluster. Thus, a cascade of transcription factors operates late in the cell cycle. Finally, the fkh1 fkh2 mutant displays a constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help control the switch to this mode of growth. Groups of assays that are related as part of a time series. Computed

2005-08-24 | E-GEOD-3182 | biostudies-arrayexpress

Cell cycle gene expression control

Project description:Gene expression data for cdc28-13 yeast released synchronously into the cell cycle. cdc28-13 yeast were arrested in G1 for 3 hours at 37 degrees. Cells were rapidly cooled to 25 C by mixing with an equal volume of media at 13 C, and time points were taken every 10 minutes. Cells were rapidly pelleted, and mRNA was isolated and hybridized against midlog mRNA.

2015-05-01 | E-GEOD-13232 | biostudies-arrayexpress

Role of the Glc7 phosphatase regulatory subunit Ypi1 in progression through mitosis

Project description:Ypi1 is an essential regulator of the Saccharomyces cerevisiae Glc7 protein phosphatase. Although lack of Ypi1 results in a dramatic blockage in the G2/M cell cycle transition, with abnormally shaped large buds and short spindles, the molecular bases for this phenotype are still obscure. We report here that depletion of Ypi1 results in stabilization of the Pds1 securin, suggesting the activation of a G2/M checkpoint. Depletion of Ypi1 in cells deleted for MAD1/MAD2 or RAD9 still resulted in G2/M blockage, in spite that these cells lack key components of the spindle assembly and DNA damage checkpoints signaling, respectively. In contrast, deletion of SWE1, which encodes a protein kinase required for the morphogenesis checkpoint signaling, allowed passage through G2/M and recovery of normal cell morphology, although eventually the cells did not survive. Depletion of Ypi1 caused stabilization of the Swe1 kinase, which resulted in persistent phosphorylation of protein kinase Cdc28 at Y19, a landmark for morphogenesis checkpoint activation. In addition, we observed that lack of Ypi1 lead to depletion of the Cdc11 septin, which explain the failure to form properly assembled septin rings at the bud necks. This defect on septin assembly is likely the origin of the activation of the morphogenesis checkpoint.

2012-12-15 | GSE23134 | GEO

4T1 RNA-Seq

Project description:Background: the transcription of tumor mutations from DNA into RNA has implications for biology, epigenetics and clinical practice. It is not clear if mutations are in general transcribed and, if so, at what proportion to the wild-type allele. Here, we examined the correlation between DNA mutation allele frequency and RNA mutation allele frequency. Methods: we sequenced the exome and transcriptome of tumor cell lines with large copy number variations, identified heterozygous single nucleotide mutations and absolute DNA copy number, and determined the corresponding DNA and RNA mutation allele fraction. Results: we found that 99% of the DNA mutations in expressed genes are expressed as RNA. Moreover, we found a high correlation between the DNA and RNA mutation allele frequency. Exceptions are mutations that cause premature termination codons and therefore activate nonsense-mediated decay. Beyond this, we did not find evidence of any wide-scale mechanism, such as allele-specific epigenetic silencing, preferentially promoting mutated or wild-type alleles. Conclusion: taken together, our data strongly suggest that genes are equally transcribed from all alleles, mutated and wild-type, and thus transcribed in proportion to their DNA allele frequency.

2014-03-05 | E-MTAB-2383 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data