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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE267291 | GEO | 2025/01/24

REPOSITORIES: GEO

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NUDT21 Negatively Regulates PSMB2 and CXXC5 by Alternative Polyadenylation and Contributes to Hepatocellular Carcinoma Suppression

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Interacting proteins of NUDT21 identified by IP-MS

Project description:Alternative polyadenylation modulates gene expresion via changing the length of 3'UTR. Among the complexes involving in APA, CFIm complex plays a central role in determining the usage of proximal PAS versus distal one. NUDT21, also named as CFIm25 and CPSF5, is the core component of CFIm complex. To date, except CPSF6 and CPSF7, there are few proteins reported to interact with NUDT21. In this project, the interactome of NUDT21 was identified by IP-MS.

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