PLX028864

GSE146867: RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Macrophages acquire a pro-inflammatory M1 phenotype in response to microbial products or pro-inflammatory cytokines through incompletely understood molecular mechanisms. We recently described the induction of APOBEC3A-mediated cellular site-specific cytosine-to-uracil (C>U) RNA editing during M1 macrophage polarization. However, the functional significance of this RNA editing is unknown. Here, we find that cellular RNA editing by APOBEC3A can also be induced by influenza or Maraba virus infections in normal macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA Seq analyses show that APOBEC3A induces C>U RNA editing (range 7%-88%) of 209 exonic or UTR sites in 203 genes during M1 polarization of monocyte-derived macrophages. The highest level of deleterious protein-recoding C>U RNA editing is observed in THOC5, which encodes a key nuclear protein implicated in the export of mRNAs during M-CSF driven macrophage differentiation. Knockdown of APOBEC3A in M1 macrophages reduces pro-inflammatory IL6, IL23A, and IL12B gene expression, CD80 and CD86 surface protein expression, and TNF-, IL-1 and IL-6 cytokine secretion, and increases glycolysis and glycolytic capacity. These results demonstrate that APOBEC3A cytidine deaminase plays an important role in transcriptomic and functional polarization of pro-inflammatory M1 macrophages. SOURCE: Eduardo Cortes (eduardo.cortesgomez@roswellpark.org) - ROSWELL PARK CANCER INSTITUTE