多囊卵巢综合征（PCOS）是最常见的生殖内分泌疾病，具有广泛的代谢影响，包括肥胖。 RNA 编辑是一种转录后修饰，可以微调蛋白质功能并引入异质性。然而，RNA编辑在PCOS中的作用及其对脂肪组织功能的影响仍知之甚少。本研究旨在利用高通量全基因组测序全面分析PCOS患者和健康对照者腹部和皮下脂肪组织中的RNA编辑事件(WGS) 和 RNA 测序。我们的结果显示，PCOS 患者表现出更多的 RNA 编辑位点，其中腺苷到肌苷 (A-to-I) 编辑很普遍。负责 A 到 I 编辑的 ADAR 基因在 PCOS 中的表达也较高。 PCOS 脂肪组织中的异常 RNA 编辑位点在免疫反应和白细胞介素 12 生物合成过程中丰富。肿瘤坏死因子 (TNF) 信号、核因子 kappa B (NF-κB) 信号、Notch 信号、末端尿苷酰转移酶 4 (TUT4)、钩微管束缚蛋白 3 (HOOK3) 和叉头盒 O1 (FOXO1) 被鉴定为的显着差异。与对照组相比，PCOS 脂肪组织中的差异表达基因（DEG）在免疫反应中富集，皮下脂肪组织和腹部脂肪组织之间的 DEG 在免疫反应中也富集，表明皮下脂肪组织的重要作用。此外，我们还确定了RNA编辑水平与特定基因的RNA表达水平之间的相关性，例如炎症通路中的共济失调毛细血管扩张突变（ATM）和粘膜相关淋巴组织淋巴瘤易位蛋白1（MALT1）以及ATM、TUT4和YTH卵母细胞发育途径中的 N6-甲基腺苷 RNA 结合蛋白 C2 (YTHDC2)。这些发现表明 PCOS 脂肪组织中的 RNA 编辑失调可能导致炎症失调。了解 RNA 编辑和脂肪组织功能之间的相互作用可能会揭示 PCOS 管理的潜在治疗靶点。然而，需要进一步的研究和验证来充分阐明这些关联背后的分子机制。版权所有 © 2024 Chen、Li、Gao、Cheng、Zhang、Liu、Chen、Liao 和 Qin。

Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood.This study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing.Our results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia-telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway.These findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.Copyright © 2024 Chen, Li, Gao, Cheng, Zhang, Liu, Chen, Liao and Qin.