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SRP078134
Homo sapiens
59 Downloadable Samples
Illumina HiSeq 2000
Description
The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One such activity is the human Nuclear EXosome Targeting (NEXT) complex, composed of hMTR4, the Zn-finger protein ZCCHC8 and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, demanding a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the PolyA tail eXosome Targeting (PAXT) connection, comprising the hitherto uncharacterized ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear polyA binding protein PABPN1. Individual depletion of ZFC3H1 and PABPN1 results in the accumulation of common transcripts, that are generally both longer and more 3'polyadenylated than NEXT substrates. Importantly, ZFC3H1/PABPN1 and ZCCHC8/RBM7 contact hMTR4 in a mutually exclusive manner, revealing that the exosome targets nuclear transcripts of different maturation status by substituting its hMTR4-associating adaptors. Overall design: RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control), RRP40, RBM7, ZCCHC8, PABPN1 and ZFC3H1. Both total and BrU RNA (one hour labeling) were collected for each condition in triplicates. The spike-in sequences used in the samples can be provided upon request.
Publication Title
Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 4000
Description
Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome-wide. We show that ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II (RNAPII) at protein-coding (pc) genes, Moreover, our results reveal a general role of ARS2 in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication dependent histone (RDH)-, promoter upstream transcript (PROMPT)- and enhancer RNA (eRNA)-loci. Depletion of the ARS2 interaction partner ZC3H18 mimics the ARS2 depletion, although to a milder extent, whereas depletion of the exosome core subunit RRP40 only impacts RNA abundance post-transcriptionally. Interestingly, ARS2 is also involved in transcription termination events within first introns of pc genes. Our work therefore establishes ARS2 as a general suppressor of pervasive transcription with the potential to regulate protein-coding gene expression. Overall design: RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control), ARS2(SRRT), ZC3H18 and CBP80. Total RNA was collected for each condition in triplicates.
Publication Title
Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Publication Title
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Illumina HiSeq 2000
Description
To uncover the gene expression alterations that occur during lung cancer progression, we interrogated the gene expression state of neoplastic cells at different stages of malignant progression. We initiated tumors in KrasLSL-G12D/+;p53flox/flox;R26LSL-tdTomato (KPT) mice with a pool of barcoded lentiviral-Cre vectors and purified Tomatopositive cancer cells away from the diverse and variable stromal cell populations. Five to nine months after tumor initiation, cancer cells were isolated from individual primary tumors and metastases using fluorescence-activated cell sorting. Sequencing of the barcode region of the integrated lentiviral vectors established primary tumor-metastasis and metastasis-metastasis relationships. Tumor barcoding allowed us to unequivocally distinguish non-metastatic primary tumors (TnonMet) from those primary tumors that had seeded metastases (TMet). We profiled 10 TnonMet samples as well as TMet and metastasis (Met) samples representing 12 metastatic events. To examine additional earlier stages of lung cancer development, we also analyzed premalignant cells from hyperplasias that develop in KPT mice shortly after tumor initiation (KPT-Early; KPT-E), as well as tumors from KrasG12D;R26LSL-tdTomato (KT) mice which rarely gain metastatic ability Overall design: This study includes 52 samples: 3 KP late samples, 3KPT early samples,10 non-metastatic primary tumors, 9 metastatic primary tumors, and 27 metastasis in different organs. total RNA was isolated and prepared for sequencing using the Ovation® RNA-Seq system and Illumina TruSeq DNA kit (v2) to generate 100bp paired end reads. Reads were aligned to mm10.
Publication Title
Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of ALR-deficient cells indicates that ALRs are not required for the IFN response to intracellular DNA. To explore whether AIM2-like receptors activated another innate signaling pathway upon
Publication Title
The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. Here, we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Using a genetic mouse model of lung adenocarcinoma, we measured the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of adhesion profiles generated using this platform differentially segregated metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. These interactions appear to be mediated in part by 31 integrin both in vitro and in vivo. We show that these galectins also correlate with human disease at both a transcriptional and histological level. Thus, our in vitro platform allowed us to interrogate the interactions of metastatic cells with their surrounding environment, and identified ECM and integrin interactions that could lead to therapeutic targets for metastasis prevention.
Publication Title
A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 308 Downloadable Samples
- Illumina HiSeq 2500
Description
One of sleep's putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, apoptosis, and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS, and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences. Overall design: Study of transcriptomic changes in three stress- and sleep-related brain regions (prefrontal cortex, hippocampus, hypothalamus) and blood following 9 weeks of Unpredictable Chronic Mild Stress (UCMS) in mice.
Publication Title
REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Chromatin architectural protein NSBP1/HMGN5 belongs to the family of HMGN proteins which specifically interact with nucleosomes via Nucleosome Binding Domain, unfold chromatin and affect transcription. Mouse NSBP1 is a new and uncharacterized member of HMGN protein family. NSBP1 is a nuclear protein which is localized to euchromatin, binds to linker histone H1 and unfolds chromatin.
Publication Title
The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 4000
Description
We describe two different routes of SCLC metastatic progression Overall design: We performed RNA-seq on primary tumors and metastasis from SCLC mouse model (Rb/p53/p130/mTmG) transduced by Ad-CMV-Cre or Ad-CGRP-Cre
Publication Title
Axon-like protrusions promote small cell lung cancer migration and metastasis.
Sample Metadata Fields
Specimen part, Subject
View Samples