Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). G4 in the mitochondrial genome are heavy-strand enriched and have been associated with the formation of deletion breakpoints that cause mitochondrial diseases. However, the functional role of G4 structures in mitochondria remains unclear. Here, we have identified RHPS4 as a G4-specific ligand that localizes to mitochondria and causes replication pausing, with mitochondrial DNA (mtDNA) depletion occurring at higher dosage. We further show that RHPS4 interferes with mitochondrial transcript elongation at low doses, leading to respiratory complex depletion. These unprecedented observations suggest that G4 motifs modulate mitochondrial transcription and replication efficiency. Using the differential effects of high vs low RHPS4 dosing, we characterized gene expression pathway responses to mitochondrial transcription inhibition or mitochondrial genome depletion. Importantly, a human mtDNA mutation that increases G4 formation potential strongly enhanced the RHPS4-mediated mitochondrial respiratory defect. We propose that abnormal G4 dynamics may contribute to mtDNA instability and gene expression defects, particularly in the presence of mitochondrial mutations that enhance the G4 formation. Overall design: Total RNA was extracted from the mouse embryonic fibroblasts (MEFs) stimulated with 0um (n=3), 2um (n=3), and 10um (n=2) RHPS4. Total stranded RNA libraries (ribo-depleted) were generated and sequenced on the Illumina NextSeq 500 NGS platform. RNA-seq data was analyzed for differentially expressed genes between groups of samples.
G-quadruplex dynamics contribute to regulation of mitochondrial gene expression.
Subject
View SamplesResearch shows that mindfulness practice can alter the expression of genes associated with energy metabolism, telomere maintenance, inflammatory and stress response. The aim of this study was to determine if mindfulness awareness practice (MAP) or health education program (HEP) might reverse cognitive impairment and/or prevent further cognitive decline in 60 subjects (aged 60-90). We investigated the gene expression changes in subject with mild cognitive impairment randomized to either group after 9 months.
Dataset on gene expression in the elderly after Mindfulness Awareness Practice or Health Education Program.
Sex, Treatment, Race
View SamplesWe were interested in characterizing the transcriptional changes that occur on a genome-wide scale following treatment of EGFR-mutant lung cancer cells with targeted therapies.
Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways.
Specimen part, Cell line, Treatment
View SamplesmiRNA abnormalities are increasingly relevent to cancer development, We used microarrays to detail the global programme of gene expression upon miR-483 overexpression in sarcoma cell line MHH-ES-1.
The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.
Disease, Disease stage
View SamplesTo investigate if biologically distinct subsets exists in extranodal NK/T-cell lymphoma (NKTL), we performed unsupervised integrative analyses of gene expression profiling (GEP), miRNA profiling, and copy number aberration (CNA) on 66 cases of NKTL from diverse anatomical sites. This series is the GEP data.
Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.
Disease, Disease stage
View SamplesIn human cells, Staufen1 is double-stranded RNA-binding protein involved in several cellular functions including mRNA localization, translation and decay. We used a genome wide approach to identify and compare the mRNA targets of mammalian Staufen1. The mRNA content of Staufen1 mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen-containing complexes following transfection of HEK293T cells with a Stau1-HA expressor. Our results indicate that 7% of the cellular RNAs expressed in HEK293T cells are found in Stau1-containing mRNPs. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes and catalytic activity.
A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes.
No sample metadata fields
View SamplesIn human cells, Staufen2 is a double-stranded RNA-binding protein involved in several cellular functions. Although 51% identical to Staufen1, these proteins are nevertheless found in different RNA particles. In addition, differential splicing events generate Staufen2 isoforms that only differ at their N-terminal extremities. We used a genome wide approach to identify and compare the mRNA targets of mammalian Staufen2 isoforms. The mRNA content of Staufen mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen2-containing complexes following transfection of HEK293T cells with Stau2-HA (59kDa) or Stau2-HA (62kDa) expressors. Our results indicate that 11% of the cellular RNAs expressed in HEK293T cells are found in Stau2-containing mRNPs. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes and catalytic activity.
A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes.
No sample metadata fields
View SamplesNext Generation Sequencing technologies have enabled de novo gene fusion discovery that could reveal candidates with therapeutic significance in cancer. Here we present an open-source software package, ChimeraScan, for the discovery of chimeric transcription between two independent transcripts. Overall design: Three cancer cell lines with known gene fusions
ChimeraScan: a tool for identifying chimeric transcription in sequencing data.
No sample metadata fields
View SamplesTumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: Primary tumors were established by direct prostate inoculation into immunosuppressed NSG mice of CE1-4 prostate cancer cells, derived from tissue-specific inactivation of PTEN [Pubmed ID: 20631921]. These cells, which were GFP-luciferase tagged, are noteworthy in that they have preserved expression of the androgen receptor and epithelial markers and recapitulate biological features of human prostate cancer. Six weeks following intra-prostate inoculation, multiple single DTCs were identified microscopically within the lungs (394 cells/hpf), with a smaller number in liver (54 cells/hpf), brain (9 cells/hpf) and bone marrow (1 cell/hpf). To undertake RNA sequencing of single cells during progression from quiescent DTCs to proliferative lesions, we identified GFP-tagged single tumor cells from lung harvested at various intervals, analyzing these separately from microdissected multicellular lesions. Individual DTCs collected at 6-7 weeks (DTC-I; N=20) and at 9-11 weeks (DTC-II; N=55) were compared with single cells derived from the primary tumor (N=29), lung micro-metastases (N=33), and CTCs isolated by microfluidic capture from blood specimens (N=12) [Pubmed ID: 28181495].
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Disease, Subject
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