Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EIF4E/mTOR-independent mRNA translation plasticity conferred by DAP5/eIF3d is required for breast cancer cell mesenchymal transition and metastasis

ABSTRACT: We report the application of polysome profiling sequencing technology for high-throughput transcriptomics and translatomics in 4T1 cells. We compare reduction of Dap5 to control in a BALB/c mouse breast cancer cell line in transcription and polysome enriched translation using RNA sequencing. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factors and their mRNA targets involved in EMT, angiogenesis, DNA repair and translation initiation, among other mRNAs. Metastatic potential of cells is significanlty decreased upon Dap5 silencing as confirmed by different in vivo models.

ORGANISM(S): Mus musculus

PROVIDER: GSE188733 | GEO | 2023/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A widespread alternate form of cap-dependent mRNA translation initiation

Project description:We report the application of polysome profiling sequencing technology for high-throughput transcriptomics and translatomics in mammalian cells. We compare reduction of Dap5 to control in metastatic breast cancer cells in transcription and polysome enriched translation using RNA sequencing. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factor and receptor capped mRNAs and their mRNA targets involved in cell survival, motility, DNA repair and translation initiation, among other mRNAs.

2018-06-30 | GSE115142 | GEO

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

DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5’ leaders

Project description:Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here, we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is required for translation initiation on select transcripts. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-dependent translation occurs on messenger RNAs (mRNAs) with long, structure-prone 5′ leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates main CDS, but not uORF, translation suggesting a role for DAP5 in translation re-initiation. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors.

2022-11-07 | GSE155854 | GEO

Identifying DAP5 mRNA translation and direct-binding targets in human embryonic stem cells (hESCs) using Ribo-seq and CLIP-seq.

Project description:The eIF4G1 DAP5 homolog is involved in several non-canonical translation initiation mechanisms. We applied ribosome profiling and found that DAP5 translationally activated mRNAs are enriched with translated uORFs. We also performed a genome-wide UV-cross linking immunoprecipitation screen (CLIP-seq) for identifying mRNAs that directly interact with DAP5 in hESCs. We found 959 bound mRNAs common to both Abs (out of 1073 and 2152 enriched mRNAs identified by CS and MBL antibodies, respectively).

2022-07-28 | GSE193115 | GEO

Proteomic investigation of the effect of DAP5 knock-down on human embryonic stem cells

Project description:We performed a deep mass-spec analysis to determine DAP5 proteomic signature on human embryonic stem cells (hESCs) by evaluating the steady state proteins level on DAP5-KD and NT control cells.

2022-08-10 | PXD030717 | Pride

Analysis of the effect of PUF3 deletion in mRNA translation in yeast

Project description:The Puf family of RNA-binding proteins regulates gene expression by controlling protein synthesis or stimulating RNA decay. Puf3p is one of six related proteins in Saccharomyces cerevisiae characterised as targeting and regulating decay of nuclear-encoded mRNAs specifying mitochondrial proteins. Much prior work has examined how Puf3p regulates COX17 mRNA. We undertook a genome-wide approach to quantitatively assess the impact of loss of PUF3 on gene expression using polysome profiling. Our translatomic study suggests that loss of Puf3p has widespread, but modest, impact on mRNA translation.

2016-03-31 | E-MTAB-3406 | biostudies-arrayexpress

Proteomic analysis of CD133 cells in the WT vs DAP5 depleted background

Project description:CD133 is a marker of cancer stem cells. DAP5 is a is a translation initiation factor. The goal of the experiment was to characterize the proteomic differences between CD133+/- cells in the WT vs DAP5 depleted background. To this aim, 4 populations of human cells were FACS sorted: shNT_CD133-, shNT CD133+, shDAP5_ CD133-, shDAP5_CD133+. The collected cell pellets were subjected to LC-MS/MS analysis.

2023-08-29 | MSV000092778 | MassIVE

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Dap5]

Project description:It has not been systematically studied whether T-cell fitness regulators uniquely or broadly contribute to specific traits limiting antitumor activity. We performed genome-scale CRISPR/Cas9 knockout screens in primary CD8 T-cells to uncover genes negatively impacting on their fitness upon three modes of stimulation: (1) intense stimulation, causing activation-induced cell death (AICD); (2) acute stimulation, triggering T-cell expansion; (3) chronic stimulation, resulting in dysfunction. Besides established regulators, we uncovered several genes controlling T-cell fitness either specifically or commonly under various stimulation modalities. Ablation of Dap5, ranking highly in all three screens, increased translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T-cell clustering amplified T-cell expansion and effector functions after both acute and intense stimulation. Finally, inactivation of Ctbp1 induced T-cell persistence exclusively upon chronic stimulation. Our results functionally annotate T-cell fitness regulators based on their unique or shared contribution to traits limiting T-cell antitumor activity.

2024-02-15 | GSE235709 | GEO

nanoCAGE reveals 5â UTR features that define specific modes of translation of functionally related mTOR-sensitive mRNAs

Project description:mTOR regulates mRNA translation. Whereas ribosome-profiling suggested that mTOR exclusively stimulates translation of TOP (containing a 5â-terminal oligopyrimidine [5âTOP] motif) and TOP-like mRNAs, polysome-profiling implied that mTOR also modulates translation of non-TOP mRNAs. We show that ribosome-, but not polysome-profiling, is biased towards identification of TOP mRNAs as differentially translated while obscuring detection of changes in non-TOP mRNA translation. Transcription start site profiling by Nano-Cap Analysis of Gene Expression (nanoCAGE) revealed that many mTOR-sensitive mRNAs do not have 5âTOP motifs. Moreover, nanoCAGE showed that 5â UTR features distinguish two functionally and translationally distinct subsets of mTOR-sensitive mRNAs: i) those with short 5â UTRs enriched for mitochondrial functions such as respiration, that are translated in an eIF4E, but not eIF4A1-dependent manner and ii) mRNAs encoding proliferation- and survival-promoting proteins, that harbor long 5â UTRs, and require both eIF4E and eIF4A1 for their efficient translation. Selective inhibition of translation of mRNAs harboring long 5â UTRs via suppression of eIF4A leads to uncoupling of expression of proteins involved in respiration (e.g. ATP5O) from those protecting mitochondrial integrity (e.g. BCL-2) ultimately resulting in apoptosis. Conversely, simultaneous translational downregulation of both long and short 5â UTR mRNAs by mTOR inhibitors results in suppression of mitochondrial respiration and predominantly cytostatic effects. Therefore, 5â UTR features define differential modes of translation of functionally distinct mTOR-sensitive mRNAs, which explains discrepancies between the effects of mTOR and eIF4A inhibitors on neoplastic cells. Determination of 5'UTR lengths using nanoCAGE in MCF7 cells

2016-03-14 | E-GEOD-77033 | biostudies-arrayexpress

Transcriptome and translatome of human regulatory T cells differentiated with TGFbeta and mTOR inhibitor everolimus

Project description: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. Using human CD4+ T cells differentiated in culture (iTregs) and genome-wide transcription and translation profiling, we show that TGFb transcriptionally reprograms naïve T cells to express iTreg differentiation and immune suppression mRNAs, while mTORC1 inhibition impairs translation of T cell mRNAs but not those induced by TGFb. TGFb-induced Treg mRNAs were found to utilize an alternate mechanism for cap-dependent mRNA translation directed by the DAP5/eIF3d complex rather than canonical mTORC1/eIF4E during Treg development, which is directed by their 5’-untranslated regions. iTreg differentiation is therefore mediated by combined TGFb transcriptional and translational reprogramming and a privileged mechanism of mRNA translation

2021-06-22 | GSE178634 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data