Assessing Microprocessor complex mutations with a Microsensor system.

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.