GEO DataSets

(Submitter supplied) Eukaryotic translation initiation factor 4E (eIF4E)–binding protein 1 (4E-BP1) inhibits cap-dependent translation in eukaryotes by competing with eIF4G for an interaction with eIF4E. Phos-phorylation at Ser-83 of 4E-BP1 occurs during mitosis through the activity of cyclin-dependent kinase 1 (CDK1)/cyclin B rather than through canonical mTOR kinase activity. Here, we investi-gated the interaction of eIF4E with 4E-BP1 or eIF4G during interphase and mitosis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

20 Samples

Download data: TXT

(Submitter supplied) Translation is a fundamental step in gene expression that regulates multiple developmental and stress responses. One key step of translation is the association between eIF4E and eIF4G. This process is regulated in different eukaryotes by proteins which bind to eIF4E and block the formation of the eIF4E/eIF4G complex. Here, we report the discovery of CERES, the first functional eIF4E regulator described in plants. more...

Organism:

Arabidopsis thaliana

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13222

18 Samples

Download data: XLS

(Submitter supplied) Ribsome profiling analysis of mRNA translation in mouse cells under conditions of mTOR activiation or inhibition.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9250

12 Samples

Download data: TXT

(Submitter supplied) Here we develop a novel methodology, capCLIP, to capture and identify mRNA interactions with the major cellular cap-binding protein eIF4E.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

8 Samples

Download data: BED, NARROWPEAK, TSV

(Submitter supplied) Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice upregulated mammalian target of rapamycin (mTOR) complex 1 signaling regulating translation, as well as cytokine protein levels. Genetic ablation of mTOR signaling showed a dual, yet contrasting effect on microglia priming: it caused an NF-kB-dependent upregulation of priming genes at mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation and milder sickness behavior. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

9 Samples

Download data: TXT

(Submitter supplied) Activation of the mechanistic target of rapamycin complex 1 (mTORC1) contributes to the development of chronic pain. However, the specific mechanisms by which mTORC1 causes hypersensitivity remain elusive. The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. Here we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

12 Samples

Download data: CSV

(Submitter supplied) We study here how mRNAs are translated in an eIF4E1-independent manner by blocking eIF4E1 using a constitutively active version of eIF4E-binding protein (4E-BP). Via ribosome profiling we identify a subset of mRNAs that are still efficiently translated when eIF4E1 is inactive. We find that these mRNAs preferentially release eIF4E1 when eIF4E1 is inactive and bind instead to eIF3D via its cap-binding pocket. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL21697

19 Samples

Download data: TXT

(Submitter supplied) High-density lipoproteins (HDLs) protect pancreatic β cells against apoptosis. This property might be related to the increased risk to develop diabetes in patients with low HDL blood levels. However, the mechanisms by which HDLs protect β cells are poorly characterized. Here we use a transcriptomic approach to identify genes differentially modulated by HDLs in β cells subjected to apoptotic stimuli.

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4026

Platform:

GPL1261

24 Samples

Download data: CEL

Analysis of pancreatic β-TC3 insulinoma cell line subjected to serum deprivation in the presence of high-density lipoproteins (HDLs). Results provide insight into the molecular mechanisms underlying the HDL protective effect on pancreatic β-cells in response to stress.

Organism:

Mus musculus

Type:

Expression profiling by array, count, 2 protocol, 2 stress sets

Platform:

GPL1261

Series:

GSE17647

24 Samples

Download data: CEL

(Submitter supplied) Regenerating pancreatic b-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of b-cell regeneration but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction that was genetically validated in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

24 Samples

Download data: TSV

(Submitter supplied) To identify which mRNAs bind to RBM4/HIF-2a

Organism:

Homo sapiens

Type:

Other

Platform:

GPL9115

2 Samples

Download data: TXT

(Submitter supplied) 4E-BP (eIF4E-BP) represses translation initiation by binding to the 5’cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used hyperTRIBE (Targets of RNA-binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. more...

Organism:

Homo sapiens; Drosophila melanogaster

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL19132

35 Samples

Download data: BW, TXT

(Submitter supplied) The oocytes of many species, both invertebrate and vertebrate, contain a large collection of localized determinants in the form of proteins and translationally inactive maternal mRNAs. However, it is unknown whether mouse oocytes contain localized MmRNA determinants and what mechanisms might be responsible for their control. We collected intact MII oocytes, enucleated MII oocyte cytoplasts (with the spindle removed), and spindle-chromosome complexes which had been microsurgically removed. more...

Organism:

Mus musculus

Type:

Expression profiling by array; Other

Platform:

GPL1261

10 Samples

Download data: CEL

(Submitter supplied) Protein synthesis is the second most energy-intensive process in the cell. Therefore, cells tightly control mRNA translation rates in response to external stimuli (growth factors, differentiation signals) and the internal resources available (nutrients, energy). We set out to unravel new molecular mechanisms of global translation control required for cellular homeostasis. Using a siRNA screening approach to knock-down all human kinases and phosphatases, we analyzed the impact of protein phosphorylation on translation regulation in unstressed, proliferating cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: CSV

(Submitter supplied) 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. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6885

8 Samples

Download data: TXT

(Submitter supplied) Cytoplasmic RNA bound to eIF4E was pulled down from MDA-MB-231 cells to determine the influence of radiation on eIF4E mRNA binding

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL571

12 Samples

Download data: CEL

(Submitter supplied) Regulatory T cells (Tregs) inhibit effector T cells and maintain immune system homeostasis. Treg maturation in peripheral sites (pTregs) is poorly understood but is known to require inhibition of protein kinase mTORC1 (e.g.RAD001) and exposure to TGFb. Paradoxically, Treg maturation requires protein synthesis yet mTORC1 inhibition downregulates it, leaving unanswered how Tregs carry-out essential mRNA translation for development and immune suppression activity. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

16 Samples

Download data: CEL

(Submitter supplied) The major cap binding protein eIF4E, an ancient protein required for translation of all eukaryotic genomes, is a surprising yet potent oncogenic driver. The genetic interactions that maintain the oncogenic activity of this key translation factor remain unknown. Here we carried out a genome-wide CRISPRi screen wherein we identified over 600 genetic interactions that sustain eIF4E oncogenic activity. Our data show that eIF4E controls the translation of Tfeb, a key executer of the autophagy response. This autophagy survival response is triggered by mitochondrial proteotoxic stress, which allows cancer cell survival. Our screen also reveals a functional interaction between eIF4E and a single anti-apoptotic factor, Bcl-xL, in tumor growth. Furthermore, we show that eIF4E and the exon-junction complex (EJC), involved in many steps of RNA metabolism, interact to control the migratory properties of cancer cells. Overall, we have uncovered several cancer-specific vulnerabilities that provide unprecedented resolution of the cancer translatome.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

24 Samples

Download data: CSV

(Submitter supplied) The mRNA cap-binding protein eIF4E1b is critical for female germline development in zebrafish. To study the effect of eIF4E1b loss in zebrafish, we isolated gonads with a high expression of ziwi:GFP (female germline marker) from wild-type and eif4e1b mutant juveniles and performed RNA-seq.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24995

6 Samples

Download data: TSV

(Submitter supplied) To investigate the mRNAs that are bound by eIF4E1b and eIF4E1c, we performed RNA immunoprecipitation (RIP) experiments using anti-GFP beads and transgenic embryos expressing GFP-eIF4E1b or GFP-eIF4E1c at the 8-cell stage.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24995

11 Samples

Download data: TSV