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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE141754 | GEO | 2021/06/01

REPOSITORIES: GEO

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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]

2021-06-02 | GSE141688 | GEO

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

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

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

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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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Computational detection of alternative exon usage.

Project description:BACKGROUND:With the advent of the GeneChip Exon Arrays, it is now possible to extract "exon-level" expression estimates, allowing for detection of alternative splicing events, one of the primary mechanisms of transcript diversity. In the context of (1) a complex trait use case and (2) a human cerebellum vs. heart comparison on previously validated data, we present a transcript-based statistical model and validation framework to allow detection of alternative exon usage (AEU) between different groups. To illustrate the approach, we detect and confirm differences in exon usage in the two of the most widely studied mouse genetic models (the C57BL/6J and DBA/2J inbred strains) and in a human dataset. RESULTS:We developed a computational framework that consists of probe level annotation mapping and statistical modeling to detect putative AEU events, as well as visualization and alignment with known splice events. We show a dramatic improvement (?25 fold) in the ability to detect these events using the appropriate annotation and statistical model which is actually specified at the transcript level, as compared with the transcript cluster/gene-level annotation used on the array. An additional component of this workflow is a probe index that allows ranking AEU candidates for validation and can aid in identification of false positives due to single nucleotide polymorphisms. DISCUSSION:Our work highlights the importance of concordance between the functional unit interrogated (e.g., gene, transcripts) and the entity (e.g., exon, probeset) within the statistical model. The framework we present is broadly applicable to other platforms (including RNAseq).

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Neuronal activity regulates alternative exon usage.

Project description:Neuronal activity-regulated gene transcription underlies plasticity-dependent changes in the molecular composition and structure of neurons. A large number of genes regulated by different neuronal plasticity inducing pathways have been identified, but altered gene expression levels represent only part of the complexity of the activity-regulated transcriptional program. Alternative splicing, the differential inclusion and exclusion of exonic sequence in mRNA, is an additional mechanism that is thought to define the activity-dependent transcriptome. Here, we present a genome wide microarray-based survey to identify exons with increased expression levels at 1, 4 or 8 h following neuronal activity in the murine hippocampus provoked by generalized seizures. We used two different bioinformatics approaches to identify alternative activity-induced exon usage and to predict alternative splicing, ANOSVA (ANalysis Of Splicing VAriation) which we here adjusted to accommodate data from different time points and FIRMA (Finding Isoforms using Robust Multichip Analysis). RNA sequencing, in situ hybridization and reverse transcription PCR validate selected activity-dependent splicing events of previously described and so far undescribed activity-regulated transcripts, including Homer1a, Homer1d, Ania3, Errfi1, Inhba, Dclk1, Rcan1, Cda, Tpm1 and Krt75. Taken together, our survey significantly adds to the comprehensive understanding of the complex activity-dependent neuronal transcriptomic signature. In addition, we provide data sets that will serve as rich resources for future comparative expression analyses.

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Neuronal activity regulates alternative exon usage

Project description:Kanate was used to induce seizures in mice, and gene expression in the hippocampus was measured

2020-11-18 | GSE148028 | GEO

Neuronal activity regulates alternative exon usage

Project description:Neuronal activity regulates alternative exon usage

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