{"doi":"10.1101/2020.03.20.988980","title":"RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization","abstract":"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-α, IL-1β 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123547,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":566837,"name":"Shraddha Sharma","orcid":null,"position":1,"is_corresponding":false},{"id":566838,"name":"A. Nazmul H. Khan","orcid":null,"position":2,"is_corresponding":false},{"id":566839,"name":"Tiffany R. Emmons","orcid":null,"position":3,"is_corresponding":false},{"id":566840,"name":"Eduardo Cortes-Gomez","orcid":null,"position":4,"is_corresponding":false},{"id":566440,"name":"Kelly L. Singel","orcid":"0000-0002-8053-4736","position":5,"is_corresponding":false},{"id":566841,"name":"Jaron Mark","orcid":null,"position":6,"is_corresponding":false},{"id":277653,"name":"Bruce A. Davidson","orcid":"0000-0001-8223-1870","position":7,"is_corresponding":false},{"id":563459,"name":"AJ Robert McGray","orcid":"0000-0002-7145-8444","position":8,"is_corresponding":false},{"id":566441,"name":"Qian Liu","orcid":"0000-0002-4517-6443","position":9,"is_corresponding":false},{"id":563461,"name":"Brian D. Lichty","orcid":"0000-0003-4514-1037","position":10,"is_corresponding":false},{"id":264808,"name":"Kirsten B. Moysich","orcid":"0000-0002-4678-2058","position":11,"is_corresponding":false},{"id":263779,"name":"Jianmin Wang","orcid":"0000-0001-7527-0409","position":12,"is_corresponding":false},{"id":32988,"name":"Kunle Odunsi","orcid":"0000-0002-4444-7651","position":13,"is_corresponding":false},{"id":243145,"name":"Brahm H. Segal","orcid":"0000-0001-5043-7380","position":14,"is_corresponding":false},{"id":566442,"name":"Bora E. Baysal","orcid":"0000-0003-3382-1545","position":15,"is_corresponding":false},{"id":566439,"name":"Emad Alqassim","orcid":"0000-0003-0765-7569","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:14:59.547352Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}