TY - JOUR
T1 - RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization
AU - Alqassim, Emad Y.
AU - Sharma, Shraddha
AU - Khan, A. N.M.Nazmul H.
AU - Emmons, Tiffany R.
AU - Cortes Gomez, Eduardo
AU - Alahmari, Abdulrahman
AU - Singel, Kelly L.
AU - Mark, Jaron
AU - Davidson, Bruce A.
AU - Robert McGray, A. J.
AU - Liu, Qian
AU - Lichty, Brian D.
AU - Moysich, Kirsten B.
AU - Wang, Jianmin
AU - Odunsi, Kunle
AU - Segal, Brahm H.
AU - Baysal, Bora E.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85099980868
U2 - 10.1038/s42003-020-01620-x
DO - 10.1038/s42003-020-01620-x
M3 - Article
C2 - 33483601
AN - SCOPUS:85099980868
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 102
ER -