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Nudt21 ablation in macrophages induces constitutive autophagy activation and diminishes inflammation in inflammatory diseases

GSE267291 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/01/24 Platform GPL24247
Summary
Macrophage hyperactivation is a hallmark of inflammatory diseases, yet the role of alternative polyadenylation (APA) in regulating innate immunity remains unclear. In this study, we demonstrate that Nudt21, a crucial RNA-binding component of the APA machinery, is significantly upregulated in various inflammatory settings. Utilizing myeloid-specific Nudt21-deficient mice, we reveal a protective effect of Nudt21 depletion against colitis and severe hyperinflammation, primarily through diminished production of proinflammatory cytokines. Notably, Nudt21 regulates the mRNA stability of key autophagy-related genes by mediating selective 3’UTR polyadenylation in activated macrophages. As a result, Nudt21-deficient macrophages display enhanced autophagic activity, which leads to reduced cytokine secretion.
Published in
Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway
Chen Y, Chen B, Li J et al. · Cellular & molecular immunology 2024 · PMID 39537902 · doi:10.1038/s41423-024-01237-8
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Also filed as BioProject PRJNA1111003 and SRA study SRP507280. Searching any of these in the dataset finder brings you back here.

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