RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • AbstractPro-inflammatory M1 macrophage polarization is associated with microbicidal and antitumor responses. We recently described APOBEC3A-mediated cytosine-to-uracil (C > U) RNA editing during M1 polarization. However, the functional significance of this editing is unknown. Here we find that APOBEC3A-mediated cellular RNA editing can also be induced by influenza or Maraba virus infections in normal human macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA_Seq analyses show that APOBEC3A mediates C>U RNA editing of 209 exonic/UTR sites in 203 genes during M1 polarization. The highest level of nonsynonymous RNA editing alters a highly-conserved amino acid in THOC5, which encodes a nuclear mRNA export protein implicated in M-CSF-driven macrophage differentiation. Knockdown of APOBEC3A reduces IL6, IL23A and IL12B gene expression, CD86 surface protein expression, and TNF-α, IL-1β and IL-6 cytokine secretion, and increases glycolysis. These results show a key role of APOBEC3A cytidine deaminase in transcriptomic and functional polarization of M1 macrophages.

authors

  • Alqassim, Emad Y
  • Sharma, Shraddha
  • Khan, ANM Nazmul H
  • Emmons, Tiffany R
  • Cortes Gomez, Eduardo
  • Alahmari, Abdulrahman
  • Singel, Kelly L
  • Mark, Jaron
  • Davidson, Bruce A
  • Robert McGray, AJ
  • Liu, Qian
  • Lichty, Brian
  • Moysich, Kirsten B
  • Wang, Jianmin
  • Odunsi, Kunle
  • Segal, Brahm H
  • Baysal, Bora E

publication date

  • December 2021