RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Pro-inflammatory M1 macrophage polarization is crucial for microbicidal and antitumor activities.
• APOBEC3A-mediated cytosine-to-uracil (C>U) RNA editing was previously observed during M1 polarization, but its functional significance remained unclear.

Purpose of the Study:

• To investigate the functional significance of APOBEC3A-mediated RNA editing in M1 macrophage polarization.
• To identify the genes and pathways regulated by APOBEC3A during M1 polarization and in response to viral infections.

Main Methods:

• Gene knockdown of APOBEC3A.
• RNA sequencing (RNA-Seq) analysis to identify edited sites and gene expression changes.
• Analysis of cytokine secretion and surface protein expression.
• Assessment of cellular glycolysis.

Main Results:

• APOBEC3A-mediated C>U RNA editing occurs in 203 genes during M1 polarization, including THOC5, a nuclear mRNA export protein.
• APOBEC3A knockdown reduced the expression of key M1-associated genes (IL6, IL23A, IL12B) and cytokines (TNF-α, IL-1β, IL-6).
• APOBEC3A knockdown also decreased CD86 surface protein expression and increased glycolysis, altering macrophage function.

Conclusions:

• APOBEC3A plays a critical role in the transcriptomic and functional polarization of M1 macrophages.
• APOBEC3A-mediated RNA editing is a significant mechanism influencing macrophage-mediated immune responses.
• APOBEC3A-mediated RNA editing can be induced by viral infections and interferons, highlighting its broader role in innate immunity.