RNA polymerase II (Pol II) is the central enzyme that carries out eukaryotic mRNA transcription and consists of a 10-subunit catalytic core and a heterodimeric subcomplex of subunits Rpb4 and Rpb7 (Rpb4/7). Rpb4/7 has been proposed to shuttle from the nucleus to the cytoplasm, and to function there in mRNA translation and degradation. Here we provide evidence that Rpb4 mainly functions in nuclear mRNA synthesis by Pol II, and evidence arguing against an important cytoplasmic role. We used metabolic RNA labeling and comparative Dynamic Transcriptome Analysis (cDTA) to show that Rpb4 deletion in Saccharomyces cerevisiae causes a drastic defect in mRNA synthesis that is compensated by down-regulation of mRNA degradation, resulting in mRNA level buffering. Deletion of Rpb4 can be rescued by covalent fusion of Rpb4 to the Pol II core subunit Rpb2, which largely restores mRNA synthesis and degradation defects caused by Rpb4 deletion. Thus Rpb4 is a bona fide Pol II core subunit which functions mainly in mRNA synthesis.
Rpb4 functions mainly in mRNA synthesis by RNA polymerase II
Sex
View SamplesDynamic transcriptome profiling with metabolic labeling (4tU) (Sun et al. Genome Research 2012) was applied to synchronized S.cerevisiae cells to estimate labeled and total mRNA levels every 5 minutes for three complete cell cycles. The dataset comprises two time series from independent biological replicates for each mRNA fraction (total, labeled).
Periodic mRNA synthesis and degradation co-operate during cell cycle gene expression
Sex, Treatment, Time
View SamplesBy applying MC EMiNEM (a novel method based on the concept of Nested Effects Models (NEMs) for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription) to the expression data from four gene perturbation studies (three of them unpublished) in Saccharomyces cerevisiae, we hope to derive new insight into the Mediator signaling network and specific transcription factor - Mediator subunit interactions. The structure of the resulting regulatory networks allows us to hypothesize on possible structural changes of the Mediator upon binding of activators or repressors.
MC EMiNEM Maps the Interaction Landscape of the Mediator
Sex
View SamplesTo identify YpdB-regulated genes, the transcriptome profiles of E. coli cells overproducing either the response regulator (RR) YpdB or the RR YehS (control) were comparatively analyzed. The expression level of 15 genes varied more than 1.9-fold.
Identification of a target gene and activating stimulus for the YpdA/YpdB histidine kinase/response regulator system in Escherichia coli
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View SamplesTo identify YehT-regulated genes, the transcriptome profiles of E. coli cells overproducing either the response regulator (RR) YehT or the RR KdpE (control) were comparatively analyzed. The expression level of 32 genes varied more than 8-fold.
First insights into the unexplored two-component system YehU/YehT in Escherichia coli
No sample metadata fields
View SamplesAnalysis of differential gene expression for rutured vs stable abdominal aortic aneurysms (AAA) and for intermediate size (55mm) vs large (>70mm) AAA.
Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Adam17 Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling in Mice.
Sex
View SamplesGene expression analysis in tissues of Adam17 hypomorphic and wildtype control C57BL/6 mice.
Adam17 Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling in Mice.
Sex
View SamplesGene expression analysis in tissues of Adam17 hypomorphic and wildtype control C57BL/6 mice.
Adam17 Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling in Mice.
Sex
View SamplesPelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo-controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid slip analysis to assess the clinical phenotype. Additionally, mRNA expression and protein accumulation as well as histological analysis of the central nervous system were performed. While Plp1 mRNA levels are increased about 1.8-fold in PMD mice compared to wildtype controls, daily Lonaprisan treatment reduced overexpression at the RNA level up to 1.5-fold, which was sufficient to significantly improve a poor motor phenotype. Electron microscopy confirmed a 25% increase in the number of myelinated axons in the corticospinal tract when compared to untreated PMD mice. Microarray analysis revealed the upregulation of pro-apoptotic genes in PMD mice that could be partially rescued by Lonaprisan treatment, which also reduced microgliosis, astrogliosis, and lymphocyte infiltration.
Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.
Sex, Age, Specimen part
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