RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization.
RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization.
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RNA编辑酶APOBEC3A促进促炎性M1巨噬细胞极化。
DOI：
10.1038/s42003-020-01620-x
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发表时间：
2021-01-22
影响因子：
5.9
通讯作者：
Baysal BE
中科院分区：
文献类型：
--
作者：
Alqassim EY;Sharma S;Khan ANMNH;Emmons TR;Cortes Gomez E;Alahmari A;Singel KL;Mark J;Davidson BA;Robert McGray AJ;Liu Q;Lichty BD;Moysich KB;Wang J;Odunsi K;Segal BH;Baysal BE
促炎性M1巨噬细胞极化与杀微生物和抗肿瘤反应相关。我们最近描述了M1极化过程中APOBEC 3A介导的胞嘧啶到尿嘧啶（C > U）RNA编辑。然而，这种编辑的功能意义尚不清楚。在这里，我们发现APOBEC 3A介导的细胞RNA编辑也可以由流感病毒或马拉巴病毒感染在正常人巨噬细胞中诱导，以及由干扰素在肿瘤相关巨噬细胞中诱导。基因敲除和RNA_Seq分析表明，APOBEC 3A在M1极化期间介导203个基因中209个外显子/UTR位点的C>U RNA编辑。最高水平的非同义RNA编辑改变了THOC 5中的高度保守氨基酸，该氨基酸编码与M-CSF驱动的巨噬细胞分化有关的核mRNA输出蛋白。敲低APOBEC 3A可降低IL 6、IL 23 A和IL 12 B基因表达、CD 86表面蛋白表达以及TNF-α、IL-1β和IL-6细胞因子分泌，并增加糖酵解。这些结果显示APOBEC 3A胞苷脱氨酶在M1巨噬细胞的转录组和功能极化中的关键作用。Alqassim等人发现，已知由IFN-1在巨噬细胞中通过酶APOBEC 3A诱导的RNA编辑是驱动M1巨噬细胞极化的转录、促炎和代谢反应所必需的。APOBEC 3A介导的编辑也由从卵巢癌相关腹水中分离的肿瘤相关巨噬细胞中的IFN-1暴露诱导，这表明APOBEC 3A在巨噬细胞中具有广泛的作用。
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. Alqassim et al find that RNA editing, known to be induced by IFN-1 in macrophages by the enzyme APOBEC3A, is required for the transcriptional, pro-inflammatory and metabolic responses that drive M1 macrophage polarization. APOBEC3A-mediated editing is also induced by IFN-1 exposure in tumor-associated macrophages isolated from ovarian cancer-related ascites fluid, pointing to a wide role for APOBEC3A in macrophages.
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影响因子：
2.7
作者：
Baysal BE;De Jong K;Liu B;Wang J;Patnaik SK;Wallace PK;Taggart RT
通讯作者：
Taggart RT
影响因子：
10.9
作者：
McGray, A. J. Robert;Huang, Ruea-Yea;Odunsi, Kunle
通讯作者：
Odunsi, Kunle
影响因子：
30.8
作者：
Chan K;Roberts SA;Klimczak LJ;Sterling JF;Saini N;Malc EP;Kim J;Kwiatkowski DJ;Fargo DC;Mieczkowski PA;Getz G;Gordenin DA
通讯作者：
Gordenin DA
DOI：
10.1084/jem.20151570
发表时间：
2016-01-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Neill LA;Pearce EJ
通讯作者：
Pearce EJ
影响因子：
12.4
作者：
Pol, Jonathan G.;Zhang, Liang;Lichty, Brian D.
通讯作者：
Lichty, Brian D.