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Identification of the long, edited dsRNAome of LPS-stimulated immune cells

ABSTRACT: Identification of the long, edited dsRNAome of LPS-stimulated immune cells

PROVIDER: PRJNA302648 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2924180_1.fastq.gz	Fastqsanger.gz
	SRR2924180_2.fastq.gz	Fastqsanger.gz
	SRR2924190_1.fastq.gz	Fastqsanger.gz
	SRR2924190_2.fastq.gz	Fastqsanger.gz
	SRR2924200_1.fastq.gz	Fastqsanger.gz

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Identification of the long, edited dsRNAome of LPS-stimulated immune cells.

Project description:Endogenous double-stranded RNA (dsRNA) must be intricately regulated in mammals to prevent aberrant activation of host inflammatory pathways by cytosolic dsRNA binding proteins. Here, we define the long, endogenous dsRNA repertoire in mammalian macrophages and monocytes during the inflammatory response to bacterial lipopolysaccharide. Hyperediting by adenosine deaminases that act on RNA (ADAR) enzymes was quantified over time using RNA-seq data from activated mouse macrophages to identify 342 Editing Enriched Regions (EERs), indicative of highly structured dsRNA. Analysis of publicly available data sets for samples of human peripheral blood monocytes resulted in discovery of 3438 EERs in the human transcriptome. Human EERs had predicted secondary structures that were significantly more stable than those of mouse EERs and were located primarily in introns, whereas nearly all mouse EERs were in 3' UTRs. Seventy-four mouse EER-associated genes contained an EER in the orthologous human gene, although nucleotide sequence and position were only rarely conserved. Among these conserved EER-associated genes were several TNF alpha-signaling genes, including Sppl2a and Tnfrsf1b, important for processing and recognition of TNF alpha, respectively. Using publicly available data and experimental validation, we found that a significant proportion of EERs accumulated in the nucleus, a strategy that may prevent aberrant activation of proinflammatory cascades in the cytoplasm. The observation of many ADAR-edited dsRNAs in mammalian immune cells, a subset of which are in orthologous genes of mouse and human, suggests a conserved role for these structured regions.

| S-EPMC4889969 | biostudies-literature

Identification of the long, edited dsRNAome of LPS-stimulated immune cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-04-12 | GSE75155 | GEO

Sequencing of LPS-stimulated immune cells from chicken

Project description:RNAs were analysed from bone marrow derived dendritic cells from 6 week old birds (control and LPS stimulated), bone marrow derived macrophages from 6 week old birds (control and LPS stimulated) and heterophils isolated from blood of day-old chicks (control and LPS stimulated).

2015-01-19 | E-MTAB-2996 | biostudies-arrayexpress

RNA-Sequencing of LPS-stimulated TLR4 HEK293 cells edited at an immune-response trans-eQTL locus

Project description:RNA-Sequencing of LPS-stimulated TLR4 HEK293 cells edited at an immune-response trans-eQTL locus

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Sequencing of LPS-stimulated immune cells from chicken

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RNA-Sequencing of LPS-stimulated TLR4 HEK293 cells edited at an immune-response trans-eQTL locus

Project description:In order to investigate the genetic effect of an IRF1-associated immune-response trans-eQTL, we used CRISPR editing to introduce deletions at the top variant rs17622517. Five unedited, three heterozygous and five homozygous clones were isolated and RNA-sequencing was performed with no stimulation, with 90min LPS stimulation and 12h LPS stimulation, with two replicates of each. We find a significant correlation between the genetic perturbation here and CRISPRi perturbation of the variant locus, as well as the trans-eQTL effects, suggesting this variant is the causal variant for the immune-response trans-eQTL.

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Global Proteomics Profiling of LPS Stimulated IMM cells

Project description:Immortalized mouse macrophages (IMMs) were stimulated with 100 ng/ml lipopolysaccharide (LPS) for 0, 30, and 60 min. The samples were analyzed using LC-MS for global proteomics.

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Glycoproteomes of naive and LPS stimulated human monocytes and THP-1 cells

Project description:CD14+ Monocytes from healthy volunteers were purified by MACS (negative selection) and FACSorting and either left untreated or stimulated for 24h and 48h with LPS. THP-1 cells were stimulated for 4h, 24h and 48h with LPS. Glycoproteins were captured with hydrazide chemistry and tryptic and PNGase F-released peptide fractions analyzed by MS/MS. Quantitative assessment revealed differential glycoprotein expression in activated/LPS-tolerized monocytes and naïve monocytes and THP-1 cells.

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Chromatin Accessibility of LPS stimulated Activated B cells

Project description:Chromatin Accessibility of LPS stimulated Activated B cells

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Identification of the long, edited dsRNAome in LPS-stimulated bone marrow-derived macrophages (BMDMs)

Project description:Endogenous double-stranded RNA (dsRNA) is intricately regulated in mammals to prevent aberrant activation of host inflammatory pathways by cytosolic dsRNA binding proteins. We define the endogenous dsRNA repertoire in mouse BMDMs during the inflammatory response to bacterial lipopolysaccharide. Editing by adenosine deaminases that act of RNA (ADAR) enzymes was quantified temporally using RNA-Seq data from activated mouse macrophages to identify 342 Editing Enriched Regions (EERs), indicative of highly structured dsRNA. Nearly all mouse EERs were present in 3’UTRs. A comparison of EERs from mouse and human revealed significant conservation of EERs between mouse EER- associated genes and homologous human genes. In addition, using publicly available data and experimental validation, a significant proportion of EERs were shown to accumulate in the nucleus, a strategy that is thought to prevent aberrant activation of proinflammatory cascades in the cytoplasm. Finally, the significant conservation of EERs and the enhancement of structured regions in human suggests an increasingly important role for these regions in human biology.

2016-04-14 | GSE75154 | GEO

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