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Inflammation drives alternative first exon usage of critical immune genes including Aim2

ABSTRACT: Inflammation drives alternative first exon usage of critical immune genes including Aim2

PROVIDER: PRJNA594622 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10620239_1.fastq.gz	Fastqsanger.gz
	SRR10620240_1.fastq.gz	Fastqsanger.gz
	SRR10620241_1.fastq.gz	Fastqsanger.gz
	SRR10620242_1.fastq.gz	Fastqsanger.gz
	SRR10620243_1.fastq.gz	Fastqsanger.gz

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Inflammation drives alternative first exon usage of critical immune genes including Aim2 [nanopore]

Project description:Inflammation drives alternative first exon usage of critical immune genes including Aim2 [nanopore]

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Inflammation drives alternative first exon usage of critical immune genes including Aim2 [RNA-seq]

Project description:Inflammation drives alternative first exon usage of critical immune genes including Aim2 [RNA-seq]

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Inflammation drives alternative first exon usage of critical immune genes including Aim2

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

2021-06-01 | GSE141754 | GEO

Inflammation drives alternative first exon usage of critical immune genes including Aim2 [nanopore]

Project description:Macrophage cells are essential components of the innate immune system and contain toll-like receptors (TLRs) that intiate the immune response when pathogen-associated molecular pattern molecules (PAMPs) are recognized. In this experiment, we stimulate TLR4 in bone marrow-derived macrophage cells with lipopolysaccharide (LPS) for 6 hours to simmulate inflammation and study the resulting differential splicing landscape and gene expression.

2021-06-02 | GSE141750 | GEO

Inflammation drives alternative first exon usage of critical immune genes including Aim2 [RNA-seq]

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Neuronal activity regulates alternative exon usage

Project description:Neuronal activity regulates alternative exon usage

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Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2.

Project description:Determining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to the isoforms produced. Of these AFE events, we identified 95 unannotated transcription start sites in mice using a de novo transcriptome generated by long-read native RNA-sequencing, one of which is in the cytosolic receptor for dsDNA and known inflammatory inducible gene, Aim2. We show that this unannotated AFE isoform of Aim2 is the predominant isoform expressed during inflammation and contains an iron-responsive element in its 5'UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response and uncovers novel regulatory mechanisms of Aim2.

| S-EPMC8260223 | biostudies-literature

Critical role for the DNA receptor AIM2 in stem-cell proliferation and cancer

Project description:Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune receptor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators were largely intact in Aim2-deficient mice, however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with wild-type healthy mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer. We used microarrays to compare the transcriptome Aim2 deficent mice to wild type mice in colon tumor and colitis samples. Here were 12 mice in total, 3 for each genotype and tissue combination.

2015-07-15 | E-GEOD-69436 | biostudies-arrayexpress

KIS counteracts PTBP2 and regulates alternative exon usage in neurons

Project description:Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

2024-04-25 | PXD050320 | Pride

Critical role for the DNA receptor AIM2 in stem-cell proliferation and cancer

2015-07-15 | GSE69436 | GEO