Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MTORC1 cooperates with tRNA wobble modification to sustain the protein synthesis machinery

ABSTRACT: mTORC1 cooperates with tRNA wobble modification to sustain the protein synthesis machinery

PROVIDER: PRJNA1054591 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR31030630.fastq.gz	Fastqsanger.gz
	SRR31030631.fastq.gz	Fastqsanger.gz
	SRR31030632.fastq.gz	Fastqsanger.gz
	SRR31030633.fastq.gz	Fastqsanger.gz
	SRR31030634.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 69

Similar Datasets

mTORC1 cooperates with tRNA wobble modification to sustain the protein synthesis machinery

Project description:Synthesizing the cellular proteome is a demanding process that is regulated by numerous signaling pathways and RNA modifications. How these orchestrate the protein synthesis machinery to generate specific proteome subsets remains unclear. We found when mTORC1 was inactive, tRNA wobble uridine-modifying enzymes (U34-enzymes) Elongator and Ctu1/2 became essential for cell growth in vitro and in tumors. Using ribosome profiling, RNA seq and other methods, we interrogated the functional interplay between U34-enzymes and mTORC1.

2025-02-19 | GSE250593 | GEO

Iron Drives Anabolic Metabolism Through Active Histone Demethylation and mTORC1

Project description:All living cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here, we report a universal eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of genes encoding high-affinity leucine transporters and RAPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency (ID) supersedes other nutrient inputs into mTORC1. This process occurs in vivo, and is not an indirect effect by canonical iron-utilizing pathways. Elevated expression of KDM3B targets is associated with reduced survival in a subset of human cancers and ID represses mTORC1 in patient-derived tumor cells and sensitizes cancer cells to chemotherapy. These data demonstrate a novel mechanism of eukaryotic iron sensing through dynamic chromatin remodeling and repression of mTORC1 mediated anabolism. Due to ancestral eukaryotes sharing homologues of KDMs and mTORC1 core components, this pathway likely predated the emergence of the other kingdom-specific nutrient sensors for mTORC1

2023-07-18 | GSE214019 | GEO

Iron Drives Anabolic Metabolism Through Active Histone Demethylation and mTORC1

Project description:All living cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here, we report a universal eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter and RAPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency (ID) supersedes other nutrient inputs into mTORC1. This process occurs in vivo, and is not an indirect effect by canonical iron-utilizing pathways. These data demonstrate a novel mechanism of eukaryotic iron sensing through dynamic chromatin remodeling and repression of mTORC1 mediated anabolism. Due to ancestral eukaryotes sharing homologues of KDMs and mTORC1 core components, this pathway likely predated the emergence of the other kingdom-specific nutrient sensors for mTORC1.

2023-07-20 | PXD043952 | Pride

Project description:Wobble tRNA modifications and mTORC1 cooperate to generate the protein synthesis machinery. (RiboSeq)

| PRJNA1053914 | ENA

Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer

Project description:Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1-dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis.analysis of transcriptomic changes due to Elp3genetic deletion in cells extracted from PyMT mammary tumors.

2016-09-29 | GSE85810 | GEO

CREBBP cooperates with cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory DLBCL

Project description:CREBBP cooperates with cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory DLBCL

| PRJNA704539 | ENA

MYC couples SWI/SNF and metabolic reprogramming to sustain minimal residual disease in mTORC1-activated cancer cells

Project description:MYC couples SWI/SNF and metabolic reprogramming to sustain minimal residual disease in mTORC1-activated cancer cells

| PRJNA1128156 | ENA

Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis

Project description:Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis

| PRJNA261727 | ENA

MYC couples SWI/SNF and metabolic reprogramming to sustain minimal residual disease in mTORC1-activated cancer cells [WES]

Project description:Therapeutics blocking PI3K-mTORC1 are commonly used for tumor treatment, and at times achieve major responses, yet minimal residual disease (MRD) persists, leading to tumor relapse. We examined the MRD models established both in vitro (Rapamycin persistent, RP) and in vivo after mTORC1 inhibition. All RP/MRD cell lines showed complete growth and signaling insensitivity to rapamycin but variable sensitivity to bi-steric mTORC1 inhibitors. MTORS2035 mutations were identified in 4 of 7 RP cell lines. Multi-omic analysis identified a pronounced shift to oxidative phosphorylation and away from glycolysis in all RP/MRD models, with increased mitochondrial number and function. MYC and SWI/SNF expression were greatly enhanced. Both the SWI/SNF inhibitor AU-15330 and the Complex I inhibitor of oxidative phosphorylation IACS-010759 showed pronounced synergy with bi-steric mTORC1 inhibitors to cause cuproptotic cell death in RP/MRD cells, suggesting these combinations as a potential patient treatment strategy for rapalog resistance.

2025-06-10 | GSE270778 | GEO

MYC couples SWI/SNF and metabolic reprogramming to sustain minimal residual disease in mTORC1-activated cancer cells [WES]

Project description:MYC couples SWI/SNF and metabolic reprogramming to sustain minimal residual disease in mTORC1-activated cancer cells [WES]

| PRJNA1128160 | ENA