Related Experiment Video
Updated: Sep 15, 2025
07:45
Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
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CFIm25-Dependent Alternative Polyadenylation in AKT2 mRNA Programs Macrophage Polarization
Srimoyee Mukherjee1, Atish Barua1, Marzieh Naseri1
1Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
CFIm25 regulates macrophage polarization by controlling alternative mRNA polyadenylation. Its overexpression promotes M1 macrophages, enhancing immune responses and cancer cell inhibition, while its knockdown favors M2 macrophages.
Area of Science:
- Immunology
- Molecular Biology
- RNA Biology
Background:
- Macrophage polarization is critical for immunity, homeostasis, and disease.
- Regulation of macrophage polarization involves complex signaling, transcription, splicing, translation, and mRNA stability.
- Alternative mRNA polyadenylation (APA) role in macrophage polarization is largely unknown.
Purpose of the Study:
- To investigate the function of CFIm25, a key APA regulator, in macrophage polarization.
- To elucidate the molecular mechanisms by which CFIm25 influences macrophage identity.
Main Methods:
- Overexpression and knockdown of CFIm25 in macrophages.
- Assessment of macrophage polarization markers (e.g., nitric oxide synthase activity, CD80 expression, cytokine secretion).
- Analysis of AKT2 mRNA polyadenylation and protein levels.
- Functional assays including phagocytosis, migration, and cancer cell inhibition.
- Antisense oligonucleotide-mediated blockade of AKT2 polyadenylation site.
Main Results:
- CFIm25 overexpression induced M1 polarization, characterized by increased pro-inflammatory markers and dampened M2 phenotype.
- CFIm25 knockdown suppressed M1 traits and promoted M2 characteristics.
- CFIm25 enhanced macrophage functions like phagocytosis, migration, and cancer cell inhibition.
- Mechanistically, CFIm25 promoted proximal polyadenylation of AKT2 mRNA, increasing Akt2 protein and supporting M1 polarization.
- Blocking the proximal AKT2 polyadenylation site reduced Akt2 expression and M1 traits.
Conclusions:
- CFIm25 is a critical regulator of macrophage polarization and identity.
- CFIm25 influences macrophage function through modulation of AKT2 mRNA polyadenylation.
- Findings provide insights into RNA-based immune regulation and potential therapeutic strategies targeting macrophage polarization.
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