Assessing Microprocessor Complex Mutations with a Microsensor System
- 1 The Hong Kong University of Science and Technology;
- 2 Hong Kong University of Science and Technology
- ↵* Corresponding author; email: tuananh{at}ust.hk
Abstract
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.
Keywords
- Received November 25, 2024.
- Accepted April 2, 2025.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
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