RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization

Author:

Alqassim Emad Y.,Sharma Shraddha,Khan A. N. M. Nazmul H.,Emmons Tiffany R.,Cortes Gomez EduardoORCID,Alahmari AbdulrahmanORCID,Singel Kelly L.,Mark Jaron,Davidson Bruce A.ORCID,Robert McGray A. J.,Liu Qian,Lichty Brian D.,Moysich Kirsten B.,Wang JianminORCID,Odunsi Kunle,Segal Brahm H.ORCID,Baysal Bora E.ORCID

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.

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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