GEO DataSets

(Submitter supplied) A novel class of translation inhibitors isolated from Aglaia plants, exemplified by Rocaglamide A (RocA), shows promise as an anti-cancer therapy. RocA converts its molecular target, translation initiation factor 4A (eIF4A), a DEAD-box protein, into a purine-selective RNA-binding protein that represses protein synthesis from a subset of mRNAs. This unusual mechanism of action raises the question of how the drug induces selectivity for polypurine sequences. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL20301

6 Samples

Download data: 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) 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:

Homo sapiens; synthetic construct

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL11154 GPL15228

23 Samples

Download data: FA, TXT

(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:

Homo sapiens; synthetic construct

Type:

Other

Platforms:

GPL21616 GPL20301

8 Samples

Download data: FA

(Submitter supplied) Small molecule compounds that inducespark the mRNA-selective translation repression, are attracting interesthave arisen due to their potential for expansion ofin druggable space expansion. However, only limited examples have been reported to datewere found. Here we showed that pateamine A (PatA) represses translation in an mRNA-selective manner by clamping eIF4A, a DEAD-box RNA-binding protein, on GNG motifs. more...

Organism:

Homo sapiens; synthetic construct

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL20301 GPL21616 GPL26697

36 Samples

Download data: CSV, 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) For the past decade, extensive studies of translation have produced a vast amount of ribosome profiling data, an insightful resource for mining of critical details about the dynamics of translation regulation under various biological contexts. Previously, Rocaglamide A (RocA), an anti-tumor heterotricyclic natural compound, has been shown to selectively inhibit translation initiation of a large group of mRNA species by clamping eukaryotic translation initiation factor 4A (eIF4A) onto poly-purine motifs in the 5’ un-translational regions (5’UTRs). more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL24676

3 Samples

Download data: TXT

(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) Eukaryotic translation initiation factor (eIF) 4A — a DEAD-box RNA-binding protein — plays an essential role in translation initiation. Recent reports have suggested helicase-dependent and helicase-independent functions for eIF4A, but the multifaceted roles of eIF4A have not been fully explored. Here, we show that eIF4A1 enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL20301

31 Samples

Download data: TXT

(Submitter supplied) 80S ribosomes of S.cerevisiae carry G2400A mutation in the 25S rRNA which makes them sensitive to macrolide antibiotics

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL13821 GPL21656

4 Samples

Download data: WIG

(Submitter supplied) Plants often generate secondary metabolites with antifungal properties as defense mechanisms against parasites. Although some fungi may potentially overcome the barrier of antimicrobial compounds, only a limited number of examples and molecular mechanisms of resistance have been reported. Here, we found an Aglaia plant-parasitizing fungus that overcomes the toxicity of rocalgates, which are translation inhibitors synthesized by the plant, through an amino acid substitution in a translation initiation factor (eIF). more...

Organism:

Colletotrichum orbiculare

Type:

Other

Platform:

GPL32115

31 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) 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) 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) 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) 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) 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) Inhibition of translation initiation using eIF4A inhibitors like (-)-didesmethylrocaglamide [(-)-DDR] and (-)-rocaglamide [(-)-Roc] is a potential cancer treatment strategy as they simultaneously diminish multiple oncogenic drivers. We showed that human and dog osteosarcoma cells expressed high levels of eIF4A1/2, which are important for cell growth. To advance preclinical development of eIF4A inhibitors, the importance of (-)-chirality in DDR for growth-inhibitory activity was demonstrated. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

15 Samples

Download data: XLSX