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Translation State Array Assay for C elegans IFE-1-dependent mRNAs

ABSTRACT: Relative polysomal loading changes for wild type (N2) versus ife-1(bn127) C. elegans strains Strain ife-1(bn127) is null for the gene encoding one of five eIF4E isoforms in the worm, IFE-1. Only this isoform associates with P granules.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE74459 | GEO | 2016/01/07

SECONDARY ACCESSION(S): PRJNA300453

REPOSITORIES: GEO

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Translation State Array Assay for C elegans IFE-1-dependent mRNAs

Project description:Relative polysomal loading changes for wild type (N2) versus ife-1(bn127) C. elegans strains Strain ife-1(bn127) is null for the gene encoding one of five eIF4E isoforms in the worm, IFE-1. Only this isoform associates with P granules. Resolution of translating and non-translating mRNAs from WT and mutant worms on 10-45% sucrose gradients. Comparision was by ratios of polysomal content. Please note that each sample data table contains raw signal directly imported from the Affymetrix files and the ratio of signals, P/(NP+P), and fold-changes were further calculated. The TSAA_overview.xls contains more datails about the TSAA procedure and 'complete_data.xlsx' contains complete TSAA data output.

2016-01-07 | E-GEOD-74459 | biostudies-arrayexpress

Epigenetic activation of a subset of mRNAs identified using polyribosome microarray analysis

Project description:Background: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5 prime capâ??binding protein, plays a major role in translational control. To understand how eIF4E affects cellular proliferation and cell survival, we identified mRNA targets that are translationally responsive to eIF4E. Methodology/ principal findings: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Induction of eIF4E expression resulted in increased translation of a defined set of mRNAs; many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growthâ??related factors. eIF4E overexpression also led to augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulumâ??mediated apoptosis. Conclusions/ significance: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a therapeutic option for the development of novel anti-cancer drugs. Keywords: time course Comparison of total and polysomal RNA upon eIF4E iinduction in NIH3T3/parental and NIH3T3/eIF4E cells Each of the following pairs were generated from one hybridization: GSM153931 GSM153932 GSM153933 GSM153934 GSM153935 GSM153936 GSM153937 GSM153938 GSM153939 GSM153940 GSM153941 GSM153942 GSM153943 GSM153944 GSM153945 GSM153946 GSM153947 GSM153948 GSM153949 GSM153950 GSM153951 GSM153952 GSM153953 GSM153954 GSM153955 GSM153956 GSM153957 GSM153958 GSM153959 GSM153960 GSM153961 GSM153962

2010-06-11 | E-GEOD-6639 | biostudies-arrayexpress

Epigenetic activation of a subset of mRNAs identified using polyribosome microarray analysis

Project description:Background: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5 prime cap–binding protein, plays a major role in translational control. To understand how eIF4E affects cellular proliferation and cell survival, we identified mRNA targets that are translationally responsive to eIF4E. Methodology/ principal findings: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Induction of eIF4E expression resulted in increased translation of a defined set of mRNAs; many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth–related factors. eIF4E overexpression also led to augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum–mediated apoptosis. Conclusions/ significance: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a therapeutic option for the development of novel anti-cancer drugs. Keywords: time course

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Crassocephalum crepidioides accession Ile-Ife HSS cDNA sequences

Project description:Crassocephalum crepidioides accession Ile-Ife HSS cDNA sequences

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eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

Project description:Translational regulation plays a critical role in cell growth and proliferation, and its dysregulation results in cancer. Aberrant expression of the mRNA 5’cap-binding protein, eIF4E, has been implicated in cancer development and progression. eIF4E activity is promoted by phosphorylation. Here we show that “knock-in” mice in which eIF4E cannot be phosphorylated are resistant to tumorigenesis in a prostate cancer model. We identify multiple candidate genes involved in the resistance to oncogenic transformation. Importantly, phosphorylation of eIF4E is increased in hormone-refractory prostate cancer, the deadliest stage of the disease. Our results highlight eIF4E phosphorylation as a critical event in tumorigenesis. Comaparison of total RNA and polysomal RNA from mouse embryo fibroblasts derived from WT and eIF4E-KI (non phosphorylatable eIF4E) mice

2010-08-17 | E-GEOD-17451 | biostudies-arrayexpress

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Identification of mRNAs with reduced ribosomal loading upon knock-down of translation factor DAP5 from hESCs.

Project description:We have generated stable human ESCs (H9) expressing control or DAP5-targeting shRNA. Polysome profiles reveal no major changes in overall translation. PolyA+ RNA and RNA accociated with heavy polysomal fractions were purified in biological duplicates and sequenced using Illumina HiSeq 2000 instrument. We identified 122 potential mRNA targets of DAP5 translation that display reduced ribosomal loading, and hence reduced translation, in the absence of DAP5.

2016-09-14 | GSE80467 | GEO

Gene expression signature of the three major epidermal differentiation compartments: interfollicular epidermis (IFE), hair follicle (HF) and sebaceous gland (SG).

Project description:There are multiple stem cells in adult mammalian epidermis, but the mechanisms controlling lineage specification are poorly understood. To identify gene expression signatures of the three major epidermal differentiation compartments we micro-dissected individual SG, IFE and HF from adult epidermis. The RNA was isolated from age and sex matched wild-type mice and performed transcriptome analysis with Affymetrix Exon microarrays We micro-dissected individual interfollicular epidermis (IFE), hair follicle (HF) and sebaceous gland (SG) from adult tail epidermis. The RNA was isolated from age and sex matched wild-type mice. Three biological replicates for each epidermal differentiation compartment were analyzed.

2017-05-16 | E-GEOD-62604 | biostudies-arrayexpress

Defining the Roles and Regulation of the GATA-factor ELT-2 in the C. elegans Endoderm

Project description:We identified genome-wide sites of occupancy for the intestine-specific transcription factor ELT-2 in L3-staged N2 worm by performing ELT-2 ChIP-seq on whole worms; we performed RNA-seq on L3-staged N2 whole worms

2016-03-30 | GSE71720 | GEO

Redefining the role of eIF4E dose in development, cancer, and protein synthesis

Project description:eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the requirement for eIF4E dose at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we surprisingly found that 50% reduction in eIF4E, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation and tumorigenesis. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for eIF4E dose specifically in translating a network of mRNAs enriched for a unique 5’UTR signature. In particular, we demonstrate that eIF4E dose is essential for translating mRNAs regulating reactive oxygen species (ROS) that fuel transformation and cancer cell survival in vivo. Therefore, mammalian cells have evolved surplus eIF4E levels that cancer cells hijack to drive a translational program supporting tumorigenesis Total cellular RNA and high MW polysome associated RNA were isolated from matched untransformed and transformed WT and Eif4e+/- MEFs for analysis on Affymetrix Mouse Gene 1.0 ST arrays. The difference in log2 RMA intensity between matched polysomal RNA and total RNA was taken to quantify translational efficiency (TE).

2015-07-01 | E-GEOD-68238 | biostudies-arrayexpress

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