Effects of cadmium and ifg-1 mutant on gene expression and mRNA splicing
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ABSTRACT:
PROVIDER: PRJNA764774 | ENA |
REPOSITORIES: ENA
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Project description:Splicing of pre-mRNA is an essential process for all eukaryotic dividing cells. Pre-mRNA splicing can be influenced by environmental factors and RNA splicing defects are implicated in numerous human diseases. To understand the genetic mechanism of RNA splicing regulation under environmental stress, we performed a genome-wide RNAi screen in C. elegans and identified suppression of protein synthesis leads to strong protection against cadmium-induced RNA splicing defects. Using a mutant with partial loss of function to the C. elegans ifg-1 gene (eIF4G), we performed RNA-sequencing and found that the levels of cadmium-induced alternative splicing observed in the wildtype is highly reduced in the ifg-1 mutant. Transcriptome analysis revealed ifg-1 mutant moderately up-regulate > 80 genes involved in RNA splicing regulation and depletion of core RNA splicing regulators abolish the ifg-1 long-lived phenotype. A secondary RNAi screen revealed depletion of sma-2 and sma-3 suppresses ifg-1’s protection against stress-induced RNA splicing protection, potentially via transcription of ifg-1 up-regulated RNA splicing regulating genes. Lastly, depletion of sma-2 and sma-3 reduces ifg-1’s long-lived phenotype. Our results propose a model where translation suppression via ifg-1 increases RNA splicing fidelity under stress by upregulating RNA splicing regulatory genes via the sma-2/3 pathway that contributes to its longevity phenotype.
2022-05-11 | GSE184491 | GEO
Project description:RNA undergoes numerous processing steps required for gene expression. Little is known about RNA homeostasis during environmental stress in metazoan cells. By studying regulation of a heavy metal-induced gene named numr-1 in C. elegans, we discovered that disruption of RNA processing acts as a signal for environmental stress. We find that NUMR-1 contains motifs common to RNA splicing factors and regulates RNA splicing in vivo. A genome-wide screen reveals that numr-1 is strongly and specifically induced by silencing of genes that function in basal RNA metabolism including subunits of the metazoan integrator complex. Human integrator processes snRNAs for functioning with splicing factors, and we find that silencing of C. elegans integrator subunits disrupts snRNA processing and causes aberrant pre-mRNA splicing. Cadmium, which also strongly induces numr-1, has the same effects on snRNA processing and pre-mRNA splicing. Lastly, we find that heat shock factor-1 is required for numr-1 induction by cadmium. Our results are consistent with a model in which disruption of integrator processing of RNA acts as a molecular damage signal initiating an adaptive stress response mediated by heat shock factor-1.
2019-06-17 | GSE129970 | GEO
Project description:Effects of cadmium and integrator complex knockdown on gene expression and mRNA splicing
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Project description:Analysis of atsf1-2 mutant seedlings for pre-mRNA splicing defect. The atsf1-2 mutant is a homozygous T-DNA insertion line isolated from a SALK line, SALK_062177. Results identify transcripts with altered alternative splicing pattern in the atsf1-2 mutant. We used microarrays to examine the transcriptome profile in the atsf1-2 mutant and identified genes of which transcript levels were changed significantly.
2014-03-31 | GSE48114 | GEO
Project description:Microarray data indicate estrogen-like effects of arsenite and cadmium
2019-10-01 | GSE136595 | GEO
Project description:Analysis of atsf1-2 mutant seedlings for pre-mRNA splicing defect. The atsf1-2 mutant is a homozygous T-DNA insertion line isolated from a SALK line, SALK_062177. Results identify transcripts with altered alternative splicing pattern in the atsf1-2 mutant. We used microarrays to examine the transcriptome profile in the atsf1-2 mutant and identified genes of which transcript levels were changed significantly. Arabidopsis seedlings were grown for 9 days under long day condition. They were then used for RNA extraction and hybridization on Affymetrix ATH1 Genome Array. Three replicates for Col-0 (control) and atsf1-2 (mutant) were compared respectively.
2014-03-31 | E-GEOD-48114 | biostudies-arrayexpress
Project description:Few works have addressed the effects provoked by the exposure to cadmium containing nanoparticles (NPs) on adult zebrafish (Danio rerio). We studied the effects of CdS NPs (5 nm) or ionic cadmium (10 µg Cd/L) after 3 and 21 d of exposure and at 6 months post-exposure (mpe). Acute toxicity was recorded after exposure to both forms of cadmium. Significant cadmium accumulation was measured in the whole fish after both treatments and autometallography showed a higher accumulation of metal in the intestine than that in the liver. Histopathological alterations, such as inflammation in gills and vacuolization in the liver, were detected after the exposure to both cadmium forms and, in a lower extent, at 6 mpe. X-ray analysis proved the presence of CdS NPs in these organs. The hepatic transcriptome analysis revealed that gene ontology terms such as “immune response” or “actin binding” were over-represented after 21 d of exposure to ionic cadmium respect to CdS NPs treatment. Exposure to CdS NPs caused a significant effect on pathways involved in the immune response and oxidative stress, while the exposure to ionic cadmium affected significantly pathways involved in DNA damage and repair and in the energetic metabolism. Oxidative damage to liver proteins was detected after the exposure to ionic cadmium, while a stronger destabilization of the hepatocyte lysosomal membrane was recorded under exposure to CdS NPs. In summary, although ionic cadmium provoked stronger effects than CdS NPs, both cadmium forms exerted an array of lethal and sublethal effects to zebrafish.
2019-05-31 | GSE89756 | GEO
Project description:Estrogen-like effects of arsenite and cadmium
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Project description:Cadmium accumulation in kidney results in an irreversible chronic toxicity, but the underlying mechanisms are not clear. Transcriptomics assay may provide insight for the involved complex molecular networks. We used Affymetrix RTA arrays to detail the global gene expression profile of kidney tissues of SD rats with chronic exposure to Cadmium, and identified distinct classes of cadmium exposure related mRNA and pathways.
2022-12-31 | GSE109849 | GEO
Project description:In a genome-wide RNAi screen to identify activators of numr-1, a cadmium responsive gene involved in RNA splicing regulation, we isolated ccf-1 as a gene that is required for cadmium-induced numr-1 activation. The ccf-1 gene encodes a deadenylase within the CCR4-NOT complex that generally serves to suppress gene expression by initiating mRNA degradation. However, a role for ccf-1 as a positive regulator of stress-induced gene expression remains to be characterized. Silencing of ccf-1 inhibits various classes of cadmium-inducible genes including several glutathione-s-transferase (gst) and heat shock protein genes. RNAi knockdown of ccf-1 significantly reduces lifespan and decreases survival in cadmium, implicating a role for ccf-1 in aging and stress protection. The ccf-1 gene is also required for resistance against acrylamide with RNAi depletion of ccf-1 inhibiting acrylamide-induced gst induction, decreasing survival in acrylamide stress, and increasing C. elegans sensitivity to acrylamide-induced neurodegeneration. Using RNA-sequencing, we observed that ccf-1 regulates ~28-35% of all genes induced by cadmium (500 out of 1802 DEG) or acrylamide (296 out of 851 DEG) by >2-fold. Clustering analysis of ccf-1 dependent cadmium or acrylamide up-regulated genes indicate significant enrichment to glutathione and cytochrome P450 metabolism, suggesting a central role for ccf-1 in regulating antioxidant defense across different stressors. Using a CCF-1::GFP translational reporter, we find that CCF-1 is broadly expressed in the intestine, muscle, and hypodemis. Interestingly, CCF-1::GFP strongly localizes to the intestinal nuclei, implicating a potential nuclear role for CCF-1 in transcriptional regulation that is distinct for its deadenylase function in the cytoplasm
2023-02-17 | GSE194057 | GEO