GEO DataSets

(Submitter supplied) Ribosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

13 Samples

Download data: TXT

(Submitter supplied) To identify mRNAs that are most translationally repressed following eIF4A inhibition and those that are relatively insensitive, polysome profiling was carried with and without eIF4A inhibition by hippuristanol treatment. Polysomal, sub-polysomal and total RNA was sequenced and we used a Bayesian model to identify mRNAs that with greatest confidence had shifted from the polysomal into the sub-polysomal fractions, from the sub-polysomal into the polysomal fractionsand those mRNAs that did not change in their polysomal to sub-polysomal ratio, following hipp treatment, which were termed eIF4A-dependent, eIF4A-antidependent and eIF4A-independent mRNAs respectively

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

18 Samples

Download data: TSV

(Submitter supplied) Translational dysregulation is an emerging hallmark of cancer, and increased activity of the mRNA helicase eIF4A is associated with poor survival in malignancies. This is believed to be due to the unwinding of secondary structures within the 5’UTRs of oncogenic mRNAs, with studies showing that in general eIF4A-dependent mRNAs have longer 5’UTRs with more stable secondary structures, yet our ability to predict eIF4A-dependency from 5’UTR properties alone remains poor. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL18573

12 Samples

Download data: TXT

(Submitter supplied) DEAD-box RNA helicases eIF4A and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. eIF4B is a cofactor for eIF4A but might also function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17342

16 Samples

Download data: CSV

(Submitter supplied) Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its mRNA selectivity is proposed to reflect highly structured 5′ UTRs that depend strongly on eIF4A-mediated unwinding. However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA. more...

Organism:

synthetic construct; Homo sapiens

Type:

Other

Platforms:

GPL21616 GPL20301

8 Samples

Download data: FA

(Submitter supplied) Rocaglamide A (RocA) typifies a novel class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), the prototypical DEAD-box RNA helicase, and its mRNA selectivity is proposed to reflect highly structured 5′ UTRs that are very dependent on eIF4A-mediated unwinding. Here, we show that secondary structure in 5′ UTRs is only a minor determinant for RocA selectivity and RocA does not repress translation by reducing eIF4A activity. more...

Organism:

synthetic construct; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL11154 GPL15228

23 Samples

Download data: FA, TXT

(Submitter supplied) Small molecule compounds that sense the nucleic acid sequences, promise the attractive venue for drug development. Such an unusual effect has been observed in the natural product Rocaglamide A (RocA) from Aglaia plant, proving to exhibit anti-tumor effects by clamping eukaryotic initiation factor (eIF) 4A onto mRNA polypurine sequences. Although eIF4A has been speculated the unique target of RocA, the insensitization of eIF4A in human cells only partially rescued the translation repression from RocA, suggesting another alternative target of this compound. more...

Organism:

synthetic construct

Type:

Other

Platform:

GPL21616

7 Samples

Download data: CSV

(Submitter supplied) Small molecule compounds that sense the nucleic acid sequences, promise the attractive venue for drug development. Such an unusual effect has been observed in the natural product Rocaglamide A (RocA) from Aglaia plant, proving to exhibit anti-tumor effects by clamping eukaryotic initiation factor (eIF) 4A onto mRNA polypurine sequences. Although eIF4A has been speculated the unique target of RocA, the insensitization of eIF4A in human cells only partially rescued the translation repression from RocA, suggesting another alternative target of this compound. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

16 Samples

Download data: TXT

(Submitter supplied) Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with limited treatment options. Although metabolic reprogramming is a hallmark of many cancers, including PDA, previous attempts to target metabolic changes therapeutically have been stymied by drug toxicity and tumour cell plasticity. Here, we show that PDA cells engage an eIF4F-dependent translation program that supports redox and central carbon metabolism. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

24 Samples

Download data: TXT

(Submitter supplied) Cooperation between FGF and WNT signaling is well documented in normal development, stem cell biology and cancer progression. However, the molecular mechanisms underlying this cooperativity remain poorly understood. In this study, we employed an inducible FGFR1 to interrogate the dynamics of RNA, ribosome occupancy and protein expression as a function of FGFR signaling in the mouse mammary gland with constitutive WNT hyperactivation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

12 Samples

Download data: CSV

(Submitter supplied) The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A/DDX2 RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of Silvestrol and related compounds. For example, eIF4A promotes T-ALL development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with Silvestrol has powerful therapeutic effects in vitro and in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

10 Samples

Download data: TXT

(Submitter supplied) DEAD-box RNA helicases eIF4A and Ded1 are believed to promote translation initiation by resolving mRNA secondary structures that impede ribosome attachment at the mRNA 5’ end or subsequent scanning of the 5’UTR, but whether they perform distinct functions or act redundantly in vivo is poorly understood. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in yeast by ribosome footprint profiling. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL13821 GPL17342

32 Samples

Download data: CSV

(Submitter supplied) Hippuristanol (Hipp) is a natural product that selectively inhibits protein synthesis by targeting eukaryotic initiation factor (eIF) 4A, a DEAD-box RNA helicase required for ribosome recruitmentt o mRNA templates. Using a CRISPR/Cas9-based variomics screen, we identify functional eIF4A1 Hipp-resistant alleles, which in turn allow us to link the translation-inhibitory and cytotoxic properties of Hipp to eIF4A1 target-engagement. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL20301

12 Samples

Download data: CSV

(Submitter supplied) Deregulation of translational control is an obligatory step in oncogenesis; however, this step has not been addressed by prior genomic and transcriptional profiling studies of cancer biology. Here we simulate the translational deregulation found in cancer by ectopically over expressing translation initiation factor eIF4E in primary human mammary epithelial cells; and examine its impact on cell biology and the pattern of ribosomal recruitment to mRNA genome wide. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4454

9 Samples

Download data: CEL

(Submitter supplied) We explored the regulation of intronic polyadenylation (IPA) isoforms by silvestrol in melanoma and T lymphocytes.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL24676

12 Samples

Download data: BED

(Submitter supplied) Cellular responses to environmental stress are frequently mediated by RNA-binding proteins (RBPs). Here, we examined global RBP dynamics in Saccharomyces cerevisiae in response to glucose starvation and heat shock. Each stress induced rapid remodeling of the RNA-protein interactome, without corresponding changes in RBP abundance. Consistent with general translation shutdown, ribosomal proteins contacting the mRNA showed decreased RNA-association. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL19756

74 Samples

Download data: BEDGRAPH, TXT

(Submitter supplied) Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all members of the rocaglate family act through similar mechanisms of action. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

10 Samples

Download data: CSV

(Submitter supplied) Pancreatic ductal adenocarcinoma (PDAC) relies on hyper-activated protein synthesis. Consistently, human and mouse PDAC lose expression of the translational repressor and mTOR target 4E-BP1. Using genome-wide polysome-profiling, we here explore mRNAs whose translational efficiencies depend on the mTOR/4E-BP1 axis in Miapaca-2 cells. This was performed by isolating cytoplasmic and efficiently translated (heavy polysome-associated) mRNAs from MiaPaca-2 cells upon PP242-mediated mTOR inhibition

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

16 Samples

Download data: CEL

(Submitter supplied) We report mTOR inhibitor Rapamycin's specific and genome-wide effect on mRNA translation. Using ribosome footprinting in pancreatic cancer cells that lack 4EBP1 expression we establish the effect of mTOR-S6-dependent mRNA translation, and identify translation programs activated following mTOR inhibition.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL11154

12 Samples

Download data: TSV

(Submitter supplied) RNA-Seq analyses polysome-bound mRNAs of glioblastoma cell line NSC11 after 10nM (-)-SDS-1-021 treatement to evaluate drug-induced changes in mRNA translation

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

6 Samples

Download data: XLSX