Ribosome assembly in eukaryotes involves the activity of hundreds of assembly factors that direct the hierarchical assembly of ribosomal proteins and numerous ribosomal RNA folding steps. However, detailed insights into the function of assembly factors and ribosomal RNA folding events are lacking. To address this, we have developed ChemModSeq, a method that combines structure probing, high throughput sequencing and statistical modeling, to quantitatively measure RNA structural rearrangements during the assembly of macromolecular complexes. By applying ChemModSeq to purified 40S assembly intermediates we obtained nucleotide-resolution maps of ribosomal RNA flexibility revealing structurally distinct assembly intermediates and mechanistic insights into assembly dynamics not readily observed in cryo-electron microscopy reconstructions. We show that RNA restructuring events coincide with the release of assembly factors and predict that completion of the head domain is required before the Rio1 kinase enters the assembly pathway. Collectively, our results suggest that 40S assembly factors regulate the timely incorporation of ribosomal proteins by delaying specific folding steps in the 3’ major domain of the 20S pre-ribosomal RNA. Overall design: Three datasets of yeast ribosomal samples subjected to different chemical modifications; 1M7 dataset contains 8 different modified samples and 2 control samples; NAI dataset contains 3 different modified samples and 2 control samples; DMS dataset contains 1 modified sample and 1 control sample. Each sample consists of at least two replicates.
Snapshots of pre-rRNA structural flexibility reveal eukaryotic 40S assembly dynamics at nucleotide resolution.
Disease, Cell line, Treatment, Subject
View SamplesHMCs were treated with CsA (4.2 M) for 0 12 and 48 hours. To exmaine global gene changes in the renal mesangium following CsA treatment in order to identify novel contributors to CsA-induced renal dysfunction
Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling.
Specimen part, Treatment
View SamplesThis study aimed to generate a comprehensive analysis of changes in the transcriptome following MNV infection. Furthermore, we aimed to perform a differential gene expression analysis between MNV infection and loxoribine (tlr7 agonist) treatment to delineate features of the host modified directly by the MNV as opposed to indirect changes induced through IFN signalling. Overall design: Transcript expression profiles of RAW264.7 cells mock infected, infected with MNV (MOI 5) or treated with loxoribine (1 mM) for 12 hrs were generated using Illumina NextSeq500.
RNA Sequencing of Murine Norovirus-Infected Cells Reveals Transcriptional Alteration of Genes Important to Viral Recognition and Antigen Presentation.
Cell line, Subject
View SamplesThe transcriptome has an abundance of information about the function of individual cells, tissues and an organism in general. Characterising the transcriptome of virus infected cells can illuminate features of the viral-host relationship that are important for pathogenesis. This study broadly aimed to quantify the host gene expression changes that occur following MNV infection. Furthermore, we aimed to identify alterations in specific biological pathways by identifying alterations in transcript abundance that increase or decrease in intensity with MNV infection over time. Overall design: Transcript expression profiles of RAW264.7 cells mock infected or infected with MNV for 4, 8, 12, 16 and 20 hours (MOI 5) were generated by RNA-sequencing using Illumina NextSeq500.
RNA Sequencing of Murine Norovirus-Infected Cells Reveals Transcriptional Alteration of Genes Important to Viral Recognition and Antigen Presentation.
Cell line, Subject, Time
View SamplesEffect of fumarase point mutation or knock-out on transcriptional profile in yeast to model hereditary leiomyomatosis and renal cell cancer (HLRCC).
Modeling tumor predisposing FH mutations in yeast: effects on fumarase activity, growth phenotype and gene expression profile.
None
Sex, Subject
View SamplesWe report our results of RNA-seq analysis on freshly isolated, sorted subsets of cytotoxic lymphocytes Overall design: RNA was isolated from sorted cells. Libraries were created using standard Illumina reagents and analyzed using a HiSeq2500.
ARID5B regulates metabolic programming in human adaptive NK cells.
Specimen part, Subject
View SamplesWe compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
Microarray analysis reveals overexpression of CD163 and HO-1 in symptomatic carotid plaques.
None
Sex, Age, Specimen part, Disease, Disease stage, Subject, Time
View SamplesRNA sequencing data of macrophages after differentiation in the presence of TPC1 thyroid cancer cell line Overall design: Co-incubation in trans-well system between TPC1 cell lines and human primary macrophages
Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages.
No sample metadata fields
View SamplesMacrophages and neutrophils are almost invariably the most abundant intratumoral immune cells, and recent studies have revealed a sinister role for these cells in limiting chemotherapy efficacy. However, how these tumor-educated myeloid cells influence chemotherapy response is incompletely understood. Targeting tumor-associated macrophages by CSF-1 receptor (CSF-1R) blockade in a pre-clinical transgenic mouse model for breast cancer improved the anti-cancer efficacy of cisplatin. Importantly, our findings reveal that macrophage blockade in combination with cisplatin treatment evokes a compensatory neutrophil response limiting the therapeutic synergy of this therapy combination. Here we characterize neutrophils and macrophages gene expression profile from the tumor of mice treated with anti-CSF-1R, Control antibody, Cisplatin/anti-CSF-1R or cisplatin/control ab. Overall design: Intervention studies combining anti-CSF1R and chemotherapy in a transgenic mouse model for breast cancer.
Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response.
Specimen part, Cell line, Subject
View SamplesSustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrial-targeted nuclear genes in concert with reduced signaling via PPAR/PGC-1 and other transcriptional regulators. In cultured myocytes Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO, but not by increasing PGC-1. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity.
Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes.
Age, Specimen part
View Samples