Related Experiment Video

Updated: Jun 7, 2025

Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
08:37

Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays

Published on: April 18, 2025

265

Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway

Yunzhu Chen1,2, Baiwen Chen1,2, Jingyu Li1,2

  • 1Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cellular & Molecular Immunology
|November 13, 2024
PubMed

Insights

Nudt21, a key factor in alternative polyadenylation, drives inflammation by suppressing autophagy in macrophages. Depleting Nudt21 protects against inflammatory diseases by boosting autophagy and reducing inflammatory cytokines.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Macrophage hyperactivation is central to inflammatory diseases.
  • The role of alternative polyadenylation (APA) in innate immunity is not well understood.
  • 3' untranslated region (3'UTR) APA is a critical post-transcriptional regulatory mechanism.

Purpose of the Study:

  • To investigate the role of Nudt21 in regulating innate immunity via 3'UTR-APA.
  • To determine the impact of Nudt21 on macrophage function and inflammatory responses.
  • To explore the connection between Nudt21, autophagy, and cytokine production.

Main Methods:

  • Utilized myeloid-specific Nudt21-deficient mice models.
  • Analyzed Nudt21 expression in various inflammatory conditions.
  • Assessed cytokine production and autophagic activity in macrophages.
  • Investigated the effect of Nudt21 on mRNA stability of autophagy-related genes (Map1lc3b, Ulk2).

Main Results:

  • Nudt21 is upregulated in inflammatory conditions and promotes hyperinflammation.
  • Nudt21 deficiency protects against colitis and severe hyperinflammation.
  • Nudt21 mediates selective 3'UTR polyadenylation of autophagy genes (Map1lc3b, Ulk2) in macrophages.
  • Nudt21-deficient macrophages exhibit enhanced autophagy and reduced proinflammatory cytokine secretion.

Conclusions:

  • Nudt21 plays a critical role in modulating macrophage autophagy through 3'UTR-APA.
  • Nudt21-mediated APA is a novel regulator of innate immunity and inflammation.
  • Targeting Nudt21-APA may offer therapeutic strategies for inflammatory diseases.
Keywords:
Nudt21alternative polyadenylationautophagyinflammationmacrophage

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