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The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFa-dependent C/EBP transcription factor axis

ABSTRACT: The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFa-dependent C/EBP transcription factor axis

PROVIDER: PRJNA740057 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14883439_1.fastq.gz	Fastqsanger.gz
	SRR14883439_2.fastq.gz	Fastqsanger.gz
	SRR14883440_1.fastq.gz	Fastqsanger.gz
	SRR14883440_2.fastq.gz	Fastqsanger.gz
	SRR14883441_1.fastq.gz	Fastqsanger.gz

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The m6A reader IMP2 directs autoimmune inflammation through an IL-17– and TNFa-dependent C/EBP transcription factor axis

Project description:The m6A reader IMP2 directs autoimmune inflammation through an IL-17– and TNFa-dependent C/EBP transcription factor axis

| PRJNA740196 | ENA

The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFa-dependent C/EBP transcription factor axis

Project description:Using IMP2-deficient mice to study the role of the RNA-binding protein (RBP) IMP2 in models of autoimmunity, namely autoimmune glomerulonephritis

2021-07-02 | GSE178710 | GEO

The m6A reader IMP2 directs autoimmune inflammation through an IL-17– and TNFa-dependent C/EBP transcription factor axis

Project description:Posttranscriptional regulation of C/EBPs through m6A/IMP2 represents a new paradigm of cytokine-driven autoimmune inflammation Using an optimized data analysis workflow, we mapped about 40 million sequence reads per sample to the mouse genome (build mm10) and identified potential differentially regulated transcripts in the MEFs of siImp2 vs siControl with an absolute fold change ≥2 and p value <0.05. Altered expression of potential genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Conclusions: Our study represents the first detailed analysis of retinal transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

2021-06-24 | GSE178725 | GEO

The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis.

Project description:Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (m6A)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m6A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m6A modification. Induction of C/EBPs is enhanced by an m6A methylase "writer" and suppressed by a demethylase "eraser." The only m6A "reader" found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m6A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F, and TNFα. RNA sequencing revealed transcriptome-wide IL-17-induced transcripts that are IMP2 influenced, and RNA immunoprecipitation sequencing identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd Lipocalin-2 (Lcn2), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2, and C/EBPβ/δ. Imp2-/- mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2 Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, posttranscriptional regulation of C/EBPs through m6A/IMP2 represents a previously unidentified paradigm of cytokine-driven autoimmune inflammation.

| S-EPMC8404281 | biostudies-literature

Next Generation Sequencing (NGS) analysis of mice pancreatic islets from control and IMP2 islet specific knockout (Rip2;IMP2).

Project description:The goal of this study is to understand how IMP2 contributes to T2D traits by regulating pancreatic beta cell growth and function. Islets from control and Rip2;IMP2 mice were generated by deep sequencing. In additon, we also perfomred IMP2 RIP-Seq to identify IMP2 targets.

2023-06-11 | GSE152424 | GEO

IMP2-TRIBE

Project description:Detection of IMP2 binding sites

| PRJEB71750 | ENA

Quantitative proteomes of Imp2 KO mouse 2-cell-stage embryos

Project description:Data showing the late 2-cell-stage, control embryos (Imp2♀+/♂+) and Imp2-knockout embryos (Imp2♀−/♂+) for HPLC MS/MS analysis. 3 replicates were performed using 330 embryos per group.

2019-11-12 | PXD010397 | Pride

IMP2/IGF2BP2 HITS-CLIP from E13.5 mouse brain

Project description:HITS-CLIP is performed for the RNA-binding protein, IMP2/IGF2BP2, from E13.5 mouse brain.

2016-06-06 | E-MTAB-3636 | biostudies-arrayexpress

IMP2 axonal localization, RNA interactome, and function in development of axon trajectories

Project description:RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurologic disease. Developing axons provide a well suited model to study RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles in axon pathfinding. However, the RNA-binding proteins involved in axon pathfinding, and their corresponding mRNA targets, are still largely unknown. Here we find that the RNA-binding protein IMP2 (Igf2bp2) is strikingly enriched in developing axon tracts, including in spinal commissural axons. We used the HITS-CLIP approach to perform a genome-wide identification of RNAs that interact directly with IMP2 in the native context of developing brain. This IMP2 interactome was highly enriched for mRNA targets related to axon guidance. Accordingly, IMP2 knockdown in the developing spinal cord led to strong defects in commissural axon trajectories at the midline intermediate target. These results reveal a highly distinctive axonal enrichment of IMP2, show that it interacts with a network of axon guidance-related mRNAs, and reveal its requirement for normal axon pathfinding during vertebrate development. CLIP-seq

2016-08-02 | E-GEOD-83822 | biostudies-arrayexpress

Illinois EBP Pilot

Project description:Illinois EBP Pilot

| PRJNA844590 | ENA