Total RNA profiles associated with DDX3 wild-type (WT) or R534H variant expression with or without sodium arsenite treatment [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70803 | GEO | 2016/04/21
SECONDARY ACCESSION(S): PRJNA289568
REPOSITORIES: GEO
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Project description:By iCLIP-seq, we demonstrated that DDX3 binds to specific sites on 18S ribosomal RNA and to messenger RNAs at 5’ leader and guanidine-rich sequences immediately upstream of ribosome-dense regions and that arsenite treatment redistributes DDX3 binding from 5'UTR to CDS, which is attenuated by DDX3 R534H.
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Project description:By using ribosome profiling, we demonstrate that catalytic activity of the RNA helicase DDX3 is generally required for mediating translation repression under stress. Intriguingly, however, a cancer-related DDX3 variant DDX3 R534H selectively preserves translation of genes encoding core nucleosome components. Additionally, DDX3 variants also shift ORF usage on select genes, such as RPLP1 and stress-response factors as an added mechanism of translation regulation during stress. Thus, DDX3 through both extensive and selective interactions with RNA and the ribosomal machinery helps to remodel the translational landscape under stress and in cancer.
2016-04-21 | GSE70802 | GEO
Project description:There is a need to develop biomarkers in alternative testing models predictive for chemically induced chronic disease in humans, preferably describing key events and their relationships in an adverse outcome pathway analysis. Epigenetic modifications, and particularly DNA methylation effects, have been implicated as a major event in susceptibility to develop chronic disease. Arsenic exposure affects large populations around the world through drinking water and industrial activities. We sought to identify epigenetic markers of arsenic exposure. We analyzed the effect of sodium arsenite on DNA methylation in Danio rerio (zebrafish) embryos using unbiased methylation profiling by high throughput sequencing.
2017-10-19 | GSE90735 | GEO
Project description:Arsenic is methylated during its metabolism, thereby depleting the intracellular methyl donor S-adenosyl-methionine, which may lead to disturbances in DNA methylation patterns Cells were exposed to sodium arsenite (NaAsO2, Sigma) at concentrations of 0.08 M-BM-5M, 0.4 M-BM-5M and 2 M-BM-5M for 1, 2 and 8 weeks. A549 arsenic dose time response study.
2014-09-17 | E-GEOD-44173 | biostudies-arrayexpress
Project description:Arsenic is methylated during its metabolism, thereby depleting the intracellular methyl donor S-adenosyl-methionine, which may lead to disturbances in DNA methylation patterns which could lead to altered gene expression Cells were exposed to sodium arsenite (NaAsO2, Sigma) at concentrations of 0.08 M-BM-5M, 0.4 M-BM-5M and 2 M-BM-5M for 1, 2 and 8 weeks.
2014-09-17 | E-GEOD-44169 | biostudies-arrayexpress
Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).
2015-05-05 | E-GEOD-60760 | biostudies-arrayexpress
Project description:DEAD-box RNA helicases are central players in RNA metabolism, however, their role in translation regulation is largely unexplored in parasitic protozoa. Here, we have investigated the role of DDX3 RNA helicase in ribosome-associated protein quality control in Leishmania. We show that ribosomes move more slowly and de novo polypeptide synthesis is reduced in cells lacking DDX3. In accordance with the slowing of ribosome speed, DDX3 depleted cells exhibit higher levels of ribosome-associated ubiquitination. Especially, ubiquitination of nascent polypeptides is enhanced upon DDX3 loss as determined by the isolation of ribosome-associated nascent chains modified either by HA-Ubiquitin or by endogenous ubiquitin using biotinylated-puromycin labeling. Consistent with increased co-translational ubiquitination, quantitative proteomics analysis revealed higher recruitment of E3 ubiquitin ligases and proteasomal components to DDX3 knockout ribosomes to eliminate aberrant nascent polypeptides. In addition, we show that cells lacking DDX3 accumulate cytosolic aggregates. This along with the higher recruitment of ribosome-associated chaperones and the improvement of translation by increasing HSP70 availability suggests that co-translational control of nascent polypeptides is impaired in the absence of DDX3. Altogether, these results highlight an important role for DDX3 in ribosome-associated quality control by reducing co-translational ubiquitination and proteotoxicity, hence allowing optimal ribosome movement and translation elongation.
2021-07-23 | PXD020667 | Pride
Project description:Studying chemical disturbances during neural differentiation of mES cells has been established as an alternative in vitro testing approach for the identification of developmental toxicants. miRNAs represent a class of small regulatory RNA molecules, which bind to target mRNAs thereby repressing their translation. Many studies have shown an essential role of miRNAs in regulation of gene expression during development and ESC differentiation. Thus, neural differentiation of ESC in vitro allows investigating the role of miRNAs in chemical-mediated developmental toxicity. We analyzed the expression of miRNAs and transcriptomics changes during neural differentiation of mESC exposed to the developmental neurotoxicant sodium valproate (VPA). A total of 110 miRNAs and 377 mRNAs were identified differently expressed in neural differentiating mES cells under VPA treatment (300µM) compared to solvent control on day 16 of differentiation. Analysis of miRNA expression revealed that valproate switches the lineage specification from neural to myogenic differentiation (upregulation of muscle-enriched miRNAs mir-206, mir-133a and mir-10a and downregulation of neuro-specific miRNAs mir-124a, mir-128 and mir-137). The findings on the miRNA level could be confirmed on mRNA level (induction of expression of myogenic regulatory factors (MRFs) as well as muscle specific genes (Actc1, calponin, myosin light chain, asporin, decorin) and repression of genes involved in neurogenesis (Otx1 and 2, Zic3, 4, 5)) as well as morphologically by immunocytochemistry. The observed results were VPA specific and most probably due to inhibition of histone deacetylase (HDAC) activity of VPA for two reasons: (i) we did not observe any induction of muscle specific miRNAs in neural differentiating ES cells exposed to the unrelated developmental neurotoxicant sodium arsenite; (ii) expression of muscle specific mir-206 and muscle enriched mir-10a was similarly increased in cells exposed to a structurally different HDAC inhibitor, trichostatin A (TSA). Furthermore, using our in vitro cell system we could confirm an aberrant expression of known VPA target genes and genes involved in neural tube closure. We conclude that miRNA expression profiling is a suitable molecular endpoint for developmental neurotoxicity. Observed lineage shift into myogenesis, where miRNAs play a significant role, could be a major developmental neurotoxical mechanism of VPA. We used microarray approach to identify altered miRNA expression in neural differentiated mES cells exposed to two known developmental neurotxicants and epigenetic active substances, sodium valproate (VPA) and sodium arsenite (As)
2016-08-01 | GSE50216 | GEO
Project description:Microarray data from G2-synchronized p53(+) and p53(-) fibroblasts before and after 3 h release from cell cycle blockade in the presence of 5 uM sodium arsenite. Experiment Overall Design: Cells expressing p53 from a tet-off regulated construct were synchronized in G2 with a two-step procedure using 24 h aphidicolin treatment for initial G1 synchronization and 12 h of Hoechst 33342 to effect a G2 blockade. During Hoechst treatment, tetracycline was added to suppress p53 in half the cultures. Cells were then released into media containing 5 µM sodium arsenite and the appropriate concentration of tetracycline to maintaining p53 expression. mRNAs were collected at 0 h and 3 h after release from G2 synchrony.
2007-11-11 | E-GEOD-7101 | biostudies-arrayexpress
Project description:Studying chemical disturbances during neural differentiation of mES cells has been established as an alternative in vitro testing approach for the identification of developmental toxicants. miRNAs represent a class of small regulatory RNA molecules, which bind to target mRNAs thereby repressing their translation. Many studies have shown an essential role of miRNAs in regulation of gene expression during development and ESC differentiation. Thus, neural differentiation of ESC in vitro allows investigating the role of miRNAs in chemical-mediated developmental toxicity. We analyzed the expression of miRNAs and transcriptomics changes during neural differentiation of mESC exposed to the developmental neurotoxicant sodium valproate (VPA). A total of 110 miRNAs and 377 mRNAs were identified differently expressed in neural differentiating mES cells under VPA treatment (300µM) compared to solvent control on day 16 of differentiation. Analysis of miRNA expression revealed that valproate switches the lineage specification from neural to myogenic differentiation (upregulation of muscle-enriched miRNAs mir-206, mir-133a and mir-10a and downregulation of neuro-specific miRNAs mir-124a, mir-128 and mir-137). The findings on the miRNA level could be confirmed on mRNA level (induction of expression of myogenic regulatory factors (MRFs) as well as muscle specific genes (Actc1, calponin, myosin light chain, asporin, decorin) and repression of genes involved in neurogenesis (Otx1 and 2, Zic3, 4, 5)) as well as morphologically by immunocytochemistry. The observed results were VPA specific and most probably due to inhibition of histone deacetylase (HDAC) activity of VPA for two reasons: (i) we did not observe any induction of muscle specific miRNAs in neural differentiating ES cells exposed to the unrelated developmental neurotoxicant sodium arsenite; (ii) expression of muscle specific mir-206 and muscle enriched mir-10a was similarly increased in cells exposed to a structurally different HDAC inhibitor, trichostatin A (TSA). Furthermore, using our in vitro cell system we could confirm an aberrant expression of known VPA target genes and genes involved in neural tube closure. We conclude that miRNA expression profiling is a suitable molecular endpoint for developmental neurotoxicity. Observed lineage shift into myogenesis, where miRNAs play a significant role, could be a major developmental neurotoxical mechanism of VPA. We used microarray approach to identify altered miRNA expression in neural differentiated mES cells exposed to two known developmental neurotxicants and epigenetic active substances, sodium valproate (VPA) and sodium arsenite (As) mES cells line W4 were induced to differnetiate to neurons under exposure to VPA and As for 16 days. RNA for microarrays was collected on day 16 of differentiation from three biological replicates of solvent controls (PBS was used as a solvent for VPA and H20 for As) or substance treated cells.
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