Small regulatory RNAs including small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide Argonaute (Ago) proteins to specific target RNAs leading to mRNA destabilization or translational repression. We recently reported the identification of Importin 8 (Imp8) as a novel component of miRNA-guided regulatory pathways. Imp8 interacts with Ago proteins and localizes to cytoplasmic processing bodies (P-bodies), structures involved in RNA metabolism. For this micro-array dataset, we used immunoprecipitations of Ago2-associated mRNAs followed by micro-array analysis. The results demonstrate that Imp8 is required for recruiting Ago protein complexes to a large set of Ago2-associated target mRNAs allowing for efficient and specific gene silencing. Therefore, we provide evidence that Imp8 is required for cytoplasmic miRNA-guided gene silencing.
Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs.
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View SamplesDuring development, thymocytes bearing a moderately self-reactive T cell receptor (TCR) can be selected to become regulatory T (Treg) cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined.
Continuous T cell receptor signals maintain a functional regulatory T cell pool.
Specimen part
View SamplesWe analysed the G-actin regulated transcriptome by gene expression analysis using previously characterised actin binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF) as well as unknown directly regulated genes.
Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.
Time
View SamplesDifferent from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast, however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing.
The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells.
Cell line
View SamplesIdentification of AP-2d target genes in the midbrain of E15 mouse embryos
AP-2δ is a crucial transcriptional regulator of the posterior midbrain.
Specimen part
View SamplesThe highly conserved protein eIF5A found in archaea and all eucaryotes uniquely contains the posttranslationally formed amino acid hypusine. Despite being essential the functions of this protein and its modification remain unclear. To gain more insight into these functions temperature sensitive mutants of the human EIF5A1 were characterized in the yeast Saccharomyces cerevisiae.
Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway.
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View SamplesTo understand how an inhibition of the mitochondrial ATP synthase affects transcriptional programming and to identify potential candidates of the signaling machinery involved in ATP synthase deficiency responses, we used oligomycin on seedling liquid cultures. Seedlings were harvested at time points 0, 1 and 4 h after the start of oligomycin and control (EtOH) treatments. Already 1 h after addition of oligomycin a total of 102 genes were more than threefold up-regulated and 14 genes were repressed, with most of them showing persistent changes. After 4 h, 580 additional genes were more than threefold up-regulated, and 152 genes were repressed by oligomycin. Several genes for alternative NAD(P)H dehydrogenases and alternative oxidases (AOX1a, AOX1d and NDA1) were up-regulated early, and additional homologs (NDA2, NDB2, NDB4 and AOX1b) followed 4 h after the start of treatment. Several genes for subunits of complex I, complex IV and the ATP synthase were induced whereas hardly any genes encoding enzymes of glycolysis and the TCA cycle changed. Additionally, four of five hallmark genes for oxidative stress were increased by oligomycin. These genes are At2g21640 (UPOX), At1g19020, At1g05340 and At1g57630 and code for proteins of unknown function. Among oxidative stress proteins with known functions, several H2O2-responsive Glutathione-S-transferases and BCS1 (CYTOCHROME BC1 SYNTHESIS) were strongly up-regulated already after 1 h. BCS1 is induced by salicylic acid and independent of other reactive oxygen signaling (ROS) pathways, such as H2O2. The results indicate that several different ROS and defense signaling pathways were induced simultaneously by oligomycin. This is further corroborated by induction of several transcription factors of the WRKY and NAC families, which have been previously implicated in coordinating cellular defense signaling.
Downregulation of the δ-subunit reduces mitochondrial ATP synthase levels, alters respiration, and restricts growth and gametophyte development in Arabidopsis.
Specimen part, Treatment
View SamplesStudy on gene expression in multifunctional protein 2 deficient mice. Liver samples of two days old mice in normal conditions are used. In total 8 arrays were hybridized corresponding to 4 KO mice and 4 WT mice Results: Cholesterol synthesis is induced and ppar alpha targets also differentially expressed between KO and WT.
Coordinate induction of PPAR alpha and SREBP2 in multifunctional protein 2 deficient mice.
No sample metadata fields
View SamplesThese arrays contain data from gonodal adipose tissue of aP2-Pex5 -/- male mice
No associated publication
Specimen part
View SamplesThese arrays contain data from hypthalamus tissue of nestin-Pex5 -/- male mice
Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system.
Specimen part
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