IRE1a silences double stranded RNA through RIDD
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA909631 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22561300_1.fastq.gz | Fastqsanger.gz | |||
| SRR22561300_2.fastq.gz | Fastqsanger.gz | |||
| SRR22561301_1.fastq.gz | Fastqsanger.gz | |||
| SRR22561301_2.fastq.gz | Fastqsanger.gz | |||
| SRR22561302_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Chemotherapy is often combined with immune checkpoint inhibitor (ICI) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers including triple-negative breast cancer (TNBC), immunologically cold tumors remain largely unresponsive due to weak chemotherapy-stimulated immune responses. The mechanisms determining the immunogenicity of chemotherapy in immunologically cold tumors remain largely unknown. Here, we identify the endoplasmic reticulum (ER) stress sensor IRE1α as a critical checkpoint that restricts the immunogenicity of taxane chemotherapy and prevents the innate immune recognition of immunologically cold TNBC. IRE1α RNase silences chemotherapy-induced double-stranded RNA (dsRNA) through RIDD (Regulated IRE1-Dependent Decay) to prevent NLRP3 inflammasome–dependent pyroptosis. Inhibition of IRE1α RNase activity with a selective RNase inhibitor ORIN1001, currently in Phase I clinical trial, allows taxane chemotherapy to induce extensive dsRNA accumulation and activate NLRP3 inflammasome–dependent gasdermin D (GSDMD) cleavage. This triggers pyroptosis and a highly effective immune response in immunologically cold TNBC.
2024-10-16 | GSE220315 | GEO
Project description:To investigate possible smRNAs linked to TMM silencing by single-stranded and double-stranded silencers, we determined sequences of smRNAs by the Illumina high-throughput sequencing platform and compared silencing efficiency of different strategies. We found that single-stranded silencer alone could promote the production of smRNAs.
2013-12-23 | GSE39398 | GEO
Project description:To investigate possible smRNAs linked to TMM silencing by single-stranded and double-stranded silencers, we determined sequences of smRNAs by the Illumina high-throughput sequencing platform and compared silencing efficiency of different strategies. We found that single-stranded silencer alone could promote the production of smRNAs. smRNA profiles of 2-week-old wide type seedlings (WT) and different silencers were generated by Illumina Genome Analyzer IIx.
2013-12-23 | E-GEOD-39398 | biostudies-arrayexpress
Project description:Single Centre, open label assignment phase II clinical study.
To evaluate the effect of oral 200mg Methylene Blue tablets (administered 8x25mg) prior to endoscopy on double stranded DNA breaks in colonic biopsy samples assessed by histone gamma H2AX analysis, compared to control biopsies.
| 2178654 | ecrin-mdr-crc
Project description:The ER-resident protein kinase/endoribonuclease IRE1 is activated through trans-autophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1a in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon stimulated protein kinase PKA, which in turn phosphorylated IRE1a at Ser724, a highly conserved site within the kinase activation domain. Blocking Ser724 phosphorylation impaired the ability of IRE1a to augment the upregulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1a was highly phosphorylated at Ser724 by PKA in mice with obesity, and silencing hepatic IRE1a markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1a integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. We used DNA microarray to analyze the transcriptomic change upon IRE1a overexpression or IRE1a depletion in primary hepatocytes, to study the changes related to IRE1a Primary hepatocytes were infected with the desired adenoviruses (Ad-EGFP, Ad-WT, Ad-S724A, Ad-shCON, Ad-shIRE1a#2) or treated with glucagon. Total cellular RNA was isolated with TRIzol (Invitrogen) and subjected to analysis by Affymetrix Mouse Genome 430 2.0 Arrays. Three experiments were independently conducted.
2011-08-30 | E-GEOD-31638 | biostudies-arrayexpress
Project description:The ER-resident protein kinase/endoribonuclease IRE1 is activated through trans-autophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1a in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon stimulated protein kinase PKA, which in turn phosphorylated IRE1a at Ser724, a highly conserved site within the kinase activation domain. Blocking Ser724 phosphorylation impaired the ability of IRE1a to augment the upregulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1a was highly phosphorylated at Ser724 by PKA in mice with obesity, and silencing hepatic IRE1a markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1a integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. We used DNA microarray to analyze the transcriptomic change upon IRE1a overexpression or IRE1a depletion in primary hepatocytes, to study the changes related to IRE1a
2011-08-31 | GSE31638 | GEO
Project description:Telomeres are the ends of linear chromosomes and consist of repetitive double- and single-stranded DNA sequences. Telomeres are bound by dedicated protein complexes, such as shelterin in mammals. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp 2 mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably, tebp 1;tebp-2 double mutant animals are synthetic sterile, with germlines showing signs of severe mitotic and meiotic arrest. These results define the first telomere-binding complex of C. elegans, including TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility.
2021-03-09 | PXD019241 | Pride
Project description:Protein UFMylation regulates ribosomal DNA double-stranded break repair
| PRJNA1067156 | ENA
Project description:IRE1a and XBP1 are key regulators of the unfolded protein response (UPR). XBP1 ablation causes profound hypolipidemia in mice, and triggers feedback activation of its upstream enzyme IRE1a, instigating regulated IRE1-dependent decay (RIDD), an mRNA degradation mechanism dependent on IRE1a's endoribonuclease activity. Comprehensive microarray analysis of XBP1 and/or IRE1a deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1a. To identify RIDD substrate mRNAs and direct XBP1 targets in the liver, we performed a comprehensive comparative microarray analysis of three groups of RNA samples: WT and XBP1 deficient mice, WT and IRE1a deficient mice untreated or injected with tunicamycin, and XBP1 deficient mice injected with luciferase or IRE1a siRNA.
2012-10-17 | E-GEOD-40515 | biostudies-arrayexpress