Protein arginine methyltransferase-1 (PRMT1) is an important epigenetic regulator of cell function and contributes to inflammation and remodeling in asthma in a cell type-specific manner. Disease-specific expression patterns of microRNAs (miRNA) are associated with chronic inflammatory lung diseases, including asthma. The de novo synthesis of miRNA depends on the transcription of primary miRNA (pri-miRNA) transcript. This study assessed the role of PRMT1 on pri-miRNA to mature miRNA process in lung epithelial cells. Human airway epithelial cells, BEAS-2B, were transfected with the PRMT1 expression plasmid pcDNA3.1-PRMT1 for 48 h. Expression profiles of miRNA were determined by small RNA deep sequencing. Comparing these miRNAs with datasets of microarrays from five asthma patients (Gene Expression Omnibus dataset), 12 miRNAs were identified that related to PRMT1 overexpression and to asthma. The overexpression or knockdown of PRMT1 modulated the expression of the asthma-related miRNAs and their pri-miRNAs. Coimmunoprecipitation showed that PRMT1 formed a complex with STAT1 or RUNX1 and thus acted as a coactivator, stimulating the transcription of pri-miRNAs. Stimulation with TGF-β1 promoted the interaction of PRMT1 with STAT1 or RUNX1, thereby upregulating the transcription of two miRNAs: let-7i and miR-423. Subsequent chromatin immunoprecipitation assays revealed that the binding of the PRMT1/STAT1 or PRMT1/RUNX1 coactivators to primary let-7i (pri-let-7i) and primary miR (pri-miR) 423 promoter was critical for pri-let-7i and pri-miR-423 transcription. This study describes a novel role of PRMT1 as a coactivator for STAT1 or RUNX1, which is essential for the transcription of pri-let-7i and pri-miR-423 in epithelial cells and might be relevant to epithelium dysfunction in asthma.

中文翻译：

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PRMT1 调节肺上皮细胞中与哮喘相关的初级微 RNA (Pri-miRNA) 加工成成熟 miRNA

蛋白精氨酸甲基转移酶-1 (PRMT1) 是细胞功能的重要表观遗传调节因子，以细胞类型特异性方式促进哮喘的炎症和重塑。microRNA (miRNA) 的疾病特异性表达模式与慢性炎症性肺病（包括哮喘）有关。miRNA 的从头合成取决于初级 miRNA (pri-miRNA) 转录本的转录。该研究评估了 PRMT1 在肺上皮细胞中 pri-miRNA 到成熟 miRNA 过程中的作用。人气道上皮细胞 BEAS-2B 用 PRMT1 表达质粒 pcDNA3.1-PRMT1 转染 48 小时。通过小RNA深度测序确定miRNA的表达谱。将这些 miRNA 与来自五名哮喘患者的微阵列数据集（基因表达综合数据集）进行比较，鉴定了 12 种与 PRMT1 过表达和哮喘相关的 miRNA。PRMT1 的过表达或敲低调节了哮喘相关 miRNA 及其 pri-miRNA 的表达。共免疫沉淀表明 PRMT1 与 STAT1 或 RUNX1 形成复合物，从而充当共激活剂，刺激 pri-miRNA 的转录。TGF-β1 的刺激促进了 PRMT1 与 STAT1 或 RUNX1 的相互作用，从而上调了两种 miRNA：let-7i 和 miR-423 的转录。随后的染色质免疫沉淀分析表明，PRMT1/STAT1 或 PRMT1/RUNX1 共激活因子与初级 let-7i (pri-let-7i) 和初级 miR (pri-miR) 423 启动子的结合对于 pri-let-7i 和 pri -miR-423 转录。本研究描述了 PRMT1 作为 STAT1 或 RUNX1 共激活剂的新作用，