| Literature DB >> 33483601 |
Shraddha Sharma1,2, A N M Nazmul H Khan3, Emad Y Alqassim4,5, Tiffany R Emmons6, Eduardo Cortes Gomez7, Abdulrahman Alahmari8,9, Kelly L Singel6,10, Jaron Mark11,12, Bruce A Davidson13, A J Robert McGray14, Qian Liu7, Brian D Lichty15, Kirsten B Moysich4, Jianmin Wang7, Kunle Odunsi6,11,14, Brahm H Segal16,17,18, Bora E Baysal19.
Abstract
Pro-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.Entities:
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Year: 2021 PMID： 33483601 PMCID： PMC7822933 DOI： 10.1038/s42003-020-01620-x
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642