Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profiling nucleo/cytoplasmic distribution of mRNAs identifies a role for the Golgi-to-ER trafficking in C9orf72 toxicity

ABSTRACT: Profiling nucleo/cytoplasmic distribution of mRNAs identifies a role for the Golgi-to-ER trafficking in C9orf72 toxicity

PROVIDER: PRJNA986091 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Profiling nucleo/cytoplasmic distribution of mRNAs identifies a role for the Golgi-to-ER trafficking in C9orf72 toxicity

Project description:Compelling evidence indicates that defects in nucleocytoplasmic transport contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). In particular, hexanucleotide (G4C2) repeat expansions in C9orf72, the most common cause of genetic ALS, have a widespread impact on the transport machinery that regulates the nucleocytoplasmic distribution of proteins and RNAs, thereby affecting their functions. We have previously reported that the expression of G4C2 hexanucleotide repeats in cultured human and mouse cells caused a marked accumulation of poly(A) mRNAs in cell nuclei, suggesting that mRNA trafficking is impaired by expanded C9orf72-ALS repeats. To further characterize the process, in this work we set out to systematically identify the specific mRNAs that are altered in their nucleocytoplasmic distribution in the presence of C9orf72-ALS repeats. Results from RNAseq profiling of nuclear and cytoplasmic RNA fractions obtained from cells expressing G4C231 repeats show a significant accumulation of mRNAs in the nuclei of G4C231 cells, further suggesting that nuclear retention of mRNAs is a major effect of C9orf72 expanded repeats expression. Interestingly, pathway analysis shows that mRNAs involved in ER-to-Golgi trafficking are particularly enriched among the identified mRNAs. Most importantly, functional studies in cultured cells and Drosophila indicate that the membrane trafficking route regulated by ARFGAP1, a GTPase-activating protein that associates with Golgi, is specifically affected by expanded C9orf72 repeats, as well as by C9orf72-related dipeptide repeat proteins (C9-DPRs), pointing to ER-to-Golgi vesicle-mediated transport as a target of C9orf72 toxicity.

2023-08-21 | GSE235448 | GEO

EXPORTIN 1A Prevents Transgene Silencing in Arabidopsis through Modulating the Nucleo-cytoplasmic Partitioning of HDA6

Project description:In eukaryotic cells, nucleo-cytoplasmic trafficking of macromolecules across the nuclear envelope is an essential process that ensures a rapid exchange of different cellular components, including proteins and RNAs, between the nucleus and cytoplasm. The significance of the nucleo-cytoplasmic trafficking of chromatin regulators in regulating DNA methylation and gene silencing is not well understood. Here, using a genetic screen, we identified XPO1A, one of the nuclear export receptors in Arabidopsis, as an anti-silencing factor that protects transgenes from transcriptional silencing. Loss-of-function of XPO1A leads to locus-specific DNA hypermethylation at transgene promoters and some endogenous loci. We found that XPO1A directly interacts with histone deacetylase HDA6 in vivo and the xpo1a mutation causes increased nuclear retention of HDA6 protein, resulting in reduced histone acetylation and enhanced transgene silencing. Our results revealed a new mechanism of epigenetic regulation through the modulation of XPO1A-dependent nucleo-cytoplasm partitioning of a chromatin regulator.

2019-01-12 | GSE119098 | GEO

bioadapt2011_cytopheno-CYTOPHENO: Nucleo-cytoplasmic co-adaptation and adaptive plant phenotypes

Project description:The cytopheno project studies cytoplasmic-nucleus interactions by characterizing cytolines (same nucleus but different cytoplasm, and conversely) at several levels (growth, germination, transcriptomic, proteomic, metabolomic) notably in response to nitrogen deficiency. For this project, there are 48 hybridizations performed as following, on leaf samples from hydroponically grown plants. bioadapt2011_cytopheno - bioadapt2011_cytopheno - Evaluation of the impact of nucleo-cytoplasmic co-adaptation disruptions on nuclear genome expression in Arabidopsis - Obtaining samples by hydroponic culture.

2020-06-17 | GSE144597 | GEO

Single-Cell Analysis Reveals Androgen Receptor Regulates ER-to-Golgi Trafficking with CREB3L2 To Drive Prostate Cancer Progression

Project description:Androgen receptor (AR) plays an essential role in normal prostate development and prostate cancer (PCa) progression. To understand the role of AR at the single-cell level, we performed single-cell transcriptome analysis on PCa cells stimulated with androgen and antiandrogen to reconstruct the dynamic and direct AR transcriptional network. Our work reveals that androgen stimulates the ER and Golgi stress response , promoting secreting protein trafficking, and inhibiting cell apoptosis. Moreover, we identify an ER-to-Golgi protein vesicle-mediated transport gene signature essential for maximal androgen-mediated ER-Golgi trafficking, cell proliferation, and association with PCa prognosis and progression. Notably, we show that AR collaborates with CREB3L2, XXX, to coordinately promote ER-Golgi trafficking of Golgi enzyme Mannosidase II and PCa cell survival. Finally, we show the inhibition of the ER-Golgi transport process with Brefeldin A leads to tumor regression. Our study collectively reveals the heterogeneity of PCa cell transcriptional response to androgen stimulation, demonstrates a functional role for increased ER-Golgi trafficking process, and provides a mechanism for how the process is augmented in PCa as well as the potential of targeting may provide novel treatment strategies.

2021-10-10 | GSE165562 | GEO

Nucleo-cytoplasmic RNA distribution responsible for maintaining neuroinflammatory microenvironment.

Project description:Nucleo-cytoplasmic RNA distribution responsible for maintaining neuroinflammatory microenvironment.

| PRJNA674859 | ENA

bioadapt2011_cytopheno-CYTOPHENO: Nucleo-cytoplasmic co-adaptation and adaptive plant phenotypes

Project description:bioadapt2011_cytopheno-CYTOPHENO: Nucleo-cytoplasmic co-adaptation and adaptive plant phenotypes

| PRJNA609729 | ENA

Nucleo-cytoplasmic partitioning of ARF proteins controls auxin responses in Arabidopsis thaliana

Project description:The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development. The AUXIN RESPONSE FACTOR (ARF) family of transcription factors regulates auxin-responsive gene expression and exhibit nuclear localization in regions of high auxin responsiveness. Here we show that activating ARF7 and ARF19 proteins accumulate in micron-sized assemblies within the cytoplasm of tissues with attenuated auxin responsiveness. The intrinsically disordered middle region and the folded PB1 interaction domain of ARFs drive protein assembly formation. Mutation of a single lysine within the PB1 domain abrogates cytoplasmic assemblies, promotes ARF nuclear localization, and results in an altered transcriptome and morphological defects. Our data suggest a model in which ARF nucleo-cytoplasmic partitioning regulates auxin responsiveness, thus providing a mechanism for cellular competence for auxin signaling.

2019-07-24 | GSE104385 | GEO

Nucleo-cytoplasmic mRNA distribution

Project description:Nuclear and cytoplasmic RNA were extracted by hypotonic cell lysis from D.-mel2 cell knock down by RNAi against dU2AF50 or with non-specific dsRNA. Keywords: other

2004-05-01 | GSE1344 | GEO

Mitotic chromosomes scale to nucleo-cytoplasmic ratio and cell size in Xenopus

Project description:Mitotic chromosomes scale to nucleo-cytoplasmic ratio and cell size in Xenopus

| PRJNA896961 | ENA

Nucleo-cytoplasmic partitioning of ARF proteins controls auxin responses in Arabidopsis thaliana

Project description:Nucleo-cytoplasmic partitioning of ARF proteins controls auxin responses in Arabidopsis thaliana

| PRJNA412513 | ENA