Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RIP-Seq of An Integrated Signaling Network Controls P-Bodies Dynamics and mRNA Translation in Human Glioblastoma

ABSTRACT: Processing (P)-bodies are cytoplasmic membrane-less condensates including translationally repressed mRNAs and proteins involved in the mRNA decay machinery. The mechanisms underlying P-bodies nucleation and mRNA decay have been largely described. However, the impact of signaling networks in P-bodies dynamics and mRNA translation is still not well understood. Here, we identify a ribonucleoprotein network assembled by the E3 ubiquitin ligase Praja2 at P-bodies that coordinates protein translation and mRNA turnover in human glioblastoma (GBM). Praja2 physically interacts and spatially colocalizes with the RNA helicase DDX6, a core component and nucleating factor of P-bodies. Stimulation of the G protein-coupled receptor (GPCR)-cAMP pathway in GBM cells induces a non-proteolytic polyubiquitylation of DDX6 by Praja2. DDX6 ubiquitylation is required for P-bodies assembly and mRNA translation repression. Interfering with DDX6 ubiquitylation or downregulation of expression markedly affects P-bodies assembly. Moreover, genetic deletion of praja2 dramatically impacts the assembly of DDX6/mRNA complexes and the amount of translating polysomes, leading to cellular senescence and GBM growth arrest. These findings identify a cAMP-driven post-transcriptional control mechanism operating at P-bodies by the ubiquitin system that profoundly impacts on mRNA translation and cancer cell growth. This regulatory system may, thus, contribute to the adaptive metabolic rewiring underlying cancer growth and drug resistance.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER:

PROVIDER: E-MTAB-14331 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP163003

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

RNA-Seq of An Integrated Signaling Network Controls P-Bodies Dynamics and mRNA Translation in Human Glioblastoma

Project description:Processing (P)-bodies are cytoplasmic membrane-less condensates including translationally repressed mRNAs and proteins involved in the mRNA decay machinery. The mechanisms underlying P-bodies nucleation and mRNA decay have been largely described. However, the impact of signaling networks in P-bodies dynamics and mRNA translation is still not well understood. Here, we identify a ribonucleoprotein network assembled by the E3 ubiquitin ligase Praja2 at P-bodies that coordinates protein translation and mRNA turnover in human glioblastoma (GBM). Praja2 physically interacts and spaBally co-localizes with the RNA helicase DDX6, a core component and nucleating factor of P-bodies. Stimulation of the G protein-coupled receptor (GPCR)-cAMP pathway in GBM cells induces a non-proteolytic polyubiquitylation of DDX6 by Praja2. DDX6 ubiquitylation is required for P-bodies assembly and mRNA translation repression. Interfering with DDX6 ubiquitylation or downregulation of expression markedly affects P-bodies assembly. Moreover, geneBc deleBon of praja2 dramatically impacts the assembly of DDX6/mRNA complexes and the amount of translating polysomes, leading to cellular senescence and GBM growth arrest. These findings identify a cAMP-driven post-transcriptional control mechanism operating at P- bodies by the ubiquitin system that profoundly impacts on mRNA translation and cancer cell growth. This regulatory system may, thus, contribute to the adaptive metabolic rewiring underlying cancer growth and drug resistance.

2025-03-30 | E-MTAB-14326 | biostudies-arrayexpress

PP-Seq of An Integrated Signaling Network Controls P-Bodies Dynamics and mRNA Translation in Human Glioblastoma

Project description:Processing (P)-bodies are cytoplasmic membrane-less condensates including translationally repressed mRNAs and proteins involved in the mRNA decay machinery. The mechanisms underlying P-bodies nucleation and mRNA decay have been largely described. However, the impact of signaling networks in P-bodies dynamics and mRNA translation is still not well understood. Here, we identify a ribonucleoprotein network assembled by the E3 ubiquitin ligase Praja2 at P-bodies that coordinates protein translation and mRNA turnover in human glioblastoma (GBM). Praja2 physically interacts and spatially colocalizes with the RNA helicase DDX6, a core component and nucleating factor of P-bodies. Stimulation of the G protein-coupled receptor (GPCR)-cAMP pathway in GBM cells induces a non-proteolytic polyubiquitylation of DDX6 by Praja2. DDX6 ubiquitylation is required for P-bodies assembly and mRNA translation repression. Interfering with DDX6 ubiquitylation or downregulation of expression markedly affects P-bodies assembly. Moreover, genetic deletion of praja2 dramatically impacts the assembly of DDX6/mRNA complexes and the amount of translating polysomes, leading to cellular senescence and GBM growth arrest. These findings identify a cAMP-driven post-transcriptional control mechanism operating at P-bodies by the ubiquitin system that profoundly impacts on mRNA translation and cancer cell growth. This regulatory system may, thus, contribute to the adaptive metabolic rewiring underlying cancer growth and drug resistance.

2025-03-30 | E-MTAB-14328 | biostudies-arrayexpress

Targeted inhibition of ubiquitin signaling reverses the metabolic reprogramming and suppresses Glioblastoma growth

Project description:Glioblastoma (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population, and the high recurrence rate and resistance to current therapeutics urgently demand a better therapy for this disease. Regulation of protein stability by the ubiquitin proteasome system (UPS) represents an important control mechanism of cell growth. Deregulation of UPS is mechanistically linked to the development and progression of a variety of human cancers, including GBM. Thus, UPS system represents a valuable target for GBM treatment. Here, we find that the E3 ligase praja2 selectively marks primary IDH1-wild type GBM. By using an integrated approach, including proteomics, transcriptomics and metabolic profiling, we identify praja2 as a main component of a signaling network that regulates cancer cell growth and metabolism. We show that praja2 binds and regulates the stability of the Kinase Suppressor of Ras 2 (KSR2) and as consequence, the activity of the downstream AMP-dependent protein kinase (AMPK) in GBM cells. By degrading KSR2, praja2 attenuates the oxidative metabolism and promotes the aerobic glycolysis (Warburg effect). Brain delivery of siRNAs targeting praja2 upregulates KSR2 and negatively impacted on GBM growth, reducing the tumor size and significantly improving the survival rate of treated mice. These data highlight the role of praja2 as an essential regulator of cancer cell metabolism, and as a preferential therapeutic target to suppress GBM growth

2022-06-29 | E-MTAB-11137 | biostudies-arrayexpress

Large-scale study of total and polysomial mRNA after DDX6 depletion in HEK293 cells

Project description:DDX6 is an abundant cytoplasmic DEAD-box RNA helicase which is involved in disparate aspects of mRNA stability and translation, leading to a confused understanding of its global function. We carried out a large-scale study of total and polysomial mRNA after DDX6 depletion to get an accurate picture of its roles in human cells.

2017-09-28 | E-MTAB-4091 | biostudies-arrayexpress

Human DDX6 regulates translation and decay of inefficiently translated mRNAs

Project description:Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrate that the human ortholog of Dhh1p, DDX6, triggers deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation- and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.

2024-01-23 | GSE231964 | GEO

DDX6 decouples translational repression from RNA degradation of miRNA targets [QuantSeq mRNA]

Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.

2018-07-25 | GSE112765 | GEO

DDX6 decouples translational repression from RNA degradation of miRNA targets [ESC EpiLC 4sU]

2018-07-25 | GSE112764 | GEO

DDX6 decouples translational repression from RNA degradation of miRNA targets [DGCR8KO Polysome]

2018-07-25 | GSE112763 | GEO

DDX6 decouples translational repression from RNA degradation of miRNA targets [DGCR8KO 4sU]

2018-07-25 | GSE112762 | GEO

DDX6 decouples translational repression from RNA degradation of miRNA targets [DDX6KO Polysome]

2018-07-25 | GSE112761 | GEO