GEO DataSets

(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) 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) 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) 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) 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) 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) 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) 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) 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) 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) RNA was isolated from material that had been subjected to immunoprecipitation (IP) from RKO cells that were either left untreated or irradiated with 20 J/m2 UVC and collected 1h later; IP assays were carried out using either an antibody recognizing RNA-binding protein TIAR, or using a control IgG1 antibody. RNA was reverse-transcribed in the presence of [alpha-33P]dCTP and the radiolabeled product used to hybridize human cDNA arrays. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL1211

12 Samples

Download data

(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) 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) Polysome profiling experiments were carried out to identify the mRNAs that have altered the translation efficiency (counts in polysomal fraction/counts in monosomal fractions) in the presence of an oligonucleotide targeting a specific region of the ribosomal RNA, to study the implication of this region in the translation of specific mRNAs

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

12 Samples

Download data: XLSX

(Submitter supplied) The fidelity of start codon recognition by ribosomes is paramount during protein synthesis. The textbook knowledge of eukaryotic translation initiation depicts 5’→3’ unidirectional migration of the pre-initiation complex (PIC) along the 5’UTR. In probing translation initiation from ultra-short 5’UTR, we report that an AUG triplet near the 5’ end can be selected via PIC backsliding. The bi-directional ribosome scanning is supported by competitive selection of closely spaced AUG codons and recognition of two initiation sites flanking an internal ribosome entry site. more...

Organism:

Mus musculus; Homo sapiens

Type:

Other

Platforms:

GPL19057 GPL17021 GPL18573

22 Samples

Download data: TXT

(Submitter supplied) The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian ortholog DDX3 are critical for translation initiation. Mutations in DDX3 are linked to tumorigenesis and intellectual disability, and the enzyme is targeted by diverse viruses. How Ded1p and its orthologs engage RNAs to impact translation initiation has been a longstanding, unresolved question. Here we show that Ded1p associates with the pre-initiation complex at the mRNA entry channel of the small ribosomal subunit and that the helicase unwinds mRNA structure ahead of the scanning pre-initiation complex. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17342 GPL21656

38 Samples

Download data: TAB, TXT

(Submitter supplied) The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here 
we identify a novel and highly conserved mechanism of translational control involving RNA structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and 
genome-wide ribosome profiling analyses we show that this mechanism, initially derived from studies 
of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in 
membrane and secreted proteins. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL19958

6 Samples

Download data: TXT