RNA 编辑是一个重要的转录后过程，它会影响基因表达，并因氨基酸取代而增加蛋白质组的多样性。最近，APOBEC3 家族已成为该机制中的重要参与者，其中 APOBEC3A (A3A) 在免疫和应激反应过程中的碱基编辑中发挥着重要作用。 APOBEC3B (A3B) 是另一个家族成员，因其在乳腺癌基因组 DNA 突变中的潜在作用而受到关注。在这项研究中，我们将诱导表达细胞模型与识别 RNA 差异变异 (DVR) 的新方法结合起来，以绘制乳腺癌细胞模型中 A3B 介导的 RNA 编辑位点。我们的研究结果表明，A3B 参与选择性 RNA 编辑，包括靶向通常在肿瘤细胞中高表达的 NEAT1 和 MALAT1 长非编码 RNA。值得注意的是，这些 RNA 的结合会隔离 A3B 并抑制 A3B 针对 RNA 和 DNA 的整体活性。 NEAT1/MALAT1 释放 A3B 导致 A3B 活性增加，但 A3A 活性降低，表明两个家族成员之间存在调节反馈循环。这项研究极大地增进了我们对 A3B 在 RNA 编辑中的作用、其机制基础及其与乳腺癌发病机制的潜在相关性的理解。© 2024。作者。

RNA editing is a crucial post-transcriptional process that influences gene expression and increases the diversity of the proteome as a result of amino acid substitution. Recently, the APOBEC3 family has emerged as a significant player in this mechanism, with APOBEC3A (A3A) having prominent roles in base editing during immune and stress responses. APOBEC3B (A3B), another family member, has gained attention for its potential role in generating genomic DNA mutations in breast cancer. In this study, we coupled an inducible expression cell model with a novel methodology for identifying differential variants in RNA (DVRs) to map A3B-mediated RNA editing sites in a breast cancer cell model. Our findings indicate that A3B engages in selective RNA editing including targeting NEAT1 and MALAT1 long non-coding RNAs that are often highly expressed in tumour cells. Notably, the binding of these RNAs sequesters A3B and suppresses global A3B activity against RNA and DNA. Release of A3B from NEAT1/MALAT1 resulted in increased A3B activity at the expense of A3A activity suggesting a regulatory feedback loop between the two family members. This research substantially advances our understanding of A3B's role in RNA editing, its mechanistic underpinnings, and its potential relevance in the pathogenesis of breast cancer.© 2024. The Author(s).