Bao Sheng, Le Thi Nhu-Y, Le Cong Truc, Tran Le Nguyen Bao, Nguyen Tuan Anh
Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong 999077, China.
Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong 999077, China
RNA. 2025 Jun 16;31(7):896-915. doi: 10.1261/rna.080338.124.
The Microprocessor complex, consisting of DROSHA and DGCR8, is essential for miRNA maturation and gene regulation. Mutations in these proteins are associated with Wilms tumor (WiT), a common pediatric kidney cancer. To explore the impact of these mutations on WiT pathogenesis, we developed the Microsensor system, a novel tool for dynamically monitoring Microprocessor activity in human cells. Using this system, we engineered HEK293T cells to express the DGCR8-E518K mutation, which was previously identified in WiT patients. Our results show that this mutation significantly impairs the Microprocessor's ability to process specific pri-miRNAs in vitro and alters the miRNA expression profiles. This study demonstrates the utility of the Microsensor system in investigating the molecular mechanisms underlying mutations related to the Microprocessor complex.
由DROSHA和DGCR8组成的微处理器复合体对于miRNA成熟和基因调控至关重要。这些蛋白质的突变与肾母细胞瘤（WiT）相关，肾母细胞瘤是一种常见的儿童肾癌。为了探究这些突变对WiT发病机制的影响，我们开发了微传感器系统，这是一种用于动态监测人类细胞中微处理器活性的新型工具。利用该系统，我们构建了表达DGCR8-E518K突变的HEK293T细胞，该突变先前在WiT患者中被鉴定出。我们的结果表明，这种突变在体外显著损害了微处理器处理特定初级miRNA的能力，并改变了miRNA表达谱。这项研究证明了微传感器系统在研究与微处理器复合体相关突变的分子机制方面的实用性。
