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

Alqassim, E. Y.; Sharma, S.; Khan, A. N. H.; Emmons, T.; Cortes-Gomez, E.; Singel, K.; Mark, J.; Davidson, B. A.; McGray, A. R.; Litchy, B. D.; Moysich, K.; Wang, J.; Odunsi, K.; Segal, B. H.; Baysal, B. E.

doi:10.1101/2020.03.20.988980

bioRxiv · 10.1101/2020.03.20.988980

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

Alqassim, E. Y.·Sharma, S.·Khan, A. N. H.·Emmons, T.·Cortes-Gomez, E.·Singel, K.·Mark, J.·Davidson, B. A.·McGray, A. R.·Litchy, B. D.·Moysich, K.·Wang, J.·Odunsi, K.·Segal, B. H.·Baysal, B. E.

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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 of 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 deleterious C>U RNA editing occurred in THOC5, encoding a nuclear mRNA export protein implicated in M-CSF-driven macrophage differentiation. Knockdown of APOBEC3A reduces pro-inflammatory M1 markers including IL6, IL23A and IL12B gene expression, CD86 surface protein expression, and TNF-, IL-1{beta} and IL-6 cytokine secretion, and increases glycolysis and glycolytic capacity. Thus, APOBEC3A cytidine deaminase plays an important role in transcriptomic and functional polarization of M1 macrophages.

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Alqassim, E. Y., Sharma, S., Khan, A. N. H., Emmons, T., Cortes-Gomez, E., Singel, K., Mark, J., Davidson, B. A., McGray, A. R., Litchy, B. D., Moysich, K., Wang, J., Odunsi, K., Segal, B. H., Baysal, B. E.. 2020-03-22. RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization. https://doi.org/10.1101/2020.03.20.988980

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