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SRP014542
Homo sapiens
6 Downloadable Samples
Illumina Genome Analyzer II
Description
So far, the annotation of translation initiation sites (TISs) has been based mostly upon bioinformatics rather than experimental evidence. We adapted ribosomal footprinting to puromycin-treated cells to generate a transcriptome-wide map of TISs in a human monocytic cell line. A neural network was trained on the ribosomal footprints at previously annotated AUG translation initiation codons (TICs), and used for the ab initio prediction of TISs in 5062 transcripts with sufficient sequence coverage. Functional interpretation suggested 2994 novel upstream open reading frames (uORFs) in the 5´ UTR (924 AUG, 2070 near-cognate codons), 1406 uORFs overlapping with the coding sequence (116 AUG, 1290 near-cognate) and 546 N-terminal protein extensions (6 AUG, 540 near-cognate). The TIS detection method was validated on the basis of previously published alternative TISs and uORFs. On average, TICs in newly annotated TISs were significantly more conserved among primates than control codons, both for AUGs (p<10-10) and near-cognate codons (p=3.8×10-3). The derived transcriptome-wide map of novel candidate TISs will help to explain how human proteome diversity is influenced by alternative translation initiation and regulation. Overall design: Examination of translational initiation in human cell lines using ribosomal footprinting
Publication Title
Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM7
Publication Title
Resting cells rely on the DNA helicase component MCM2 to build cilia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues. Overall design: 6 samples in total: 3 control, 3 siRNA MCM2
Publication Title
Resting cells rely on the DNA helicase component MCM2 to build cilia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 132 Downloadable Samples
- IlluminaHiSeq1500
Description
To understand better the factors contributing to keratoconus (KTCN), we used RNA sequencing to perform a transcriptome profile of human KTCN corneas. Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-ß, Hippo, and Wnt signaling pathways influencing corneal organization. We identified long noncoding RNAs (lncRNAs) and conducted a computational analysis of their potential functions, and found that lncRNAs regulated the processing and expression of the aforementioned genes. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN. Overall design: Transcription profiling of 25 KTCN and 25 non-KTCN corneas using RNA-Seq
Publication Title
Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD14+ human monocytes differentiating into DCs in the presence of IL4 and GM-CSF were treated with agonists for RXR and its partners or vehicle 18 hours after plating (experiment with RXR and permissive partners, donor 1-3) or 14 hours after plating (experiment with nonpermissive partners, donor 4-6). Cells were harvested 12 hours thereafter. Experiments were performed in biological triplicates representing samples from three different donors.
Publication Title
Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study transcriptome profiling of dendritic cell subtypes was performed using various human dendritic cells.
Publication Title
Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease.
Publication Title
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Adropin is a multifunctional peptide hormone encoded by the ENHO (energy homeostasis associated) gene. It plays a role in mechanisms related to increased adiposity, insulin resistance, as well as glucose and lipid metabolism. The low adropin levels are strongly associated with obesity independent insulin resistance. On the other hand, overexpression or exogenous administration of adropin improves glucose homeostasis. The multidirectional, adropin-related effects associated with the regulation of metabolism in humans also appear to be attributable to the effects of this peptide on the activity of various elements of the endocrine system including adrenal cortex. Therefore, the main purpose of the present study was to investigate the effect of adropin on proliferation and secretory activity in the human HAC15 adrenal carcinoma cell line.
Publication Title
Adropin Stimulates Proliferation and Inhibits Adrenocortical Steroidogenesis in the Human Adrenal Carcinoma (HAC15) Cell Line.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Cells use their wide variety of RNPs to integrate the expression of functionally inter-related proteins by forming RNP complexes with cis-elements that are shared among co-regulated RNAs. In this study, we identified the the associated mRNAs that co-precipitated with hnRNP K in developing juvenile frog brain.
Publication Title
hnRNP K post-transcriptionally co-regulates multiple cytoskeletal genes needed for axonogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to a model hepatotoxicant cyclosporin A (CsA). It was anticipated that Fxr deficiency could aggravate toxicity of CsA in PCLS and pinpoint to novel genes/processes regulated by FXR.
Publication Title
Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions.
Sample Metadata Fields
No sample metadata fields
View Samples