Assessing Microprocessor complex mutations with a Microsensor system
- 1Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong 999077, China
- 2HKUST Shenzhen Research Institute, Shenzhen 518057, China
- Corresponding author: tuananh{at}ust.hk
-
↵3 These authors contributed equally to this work.
-
Handling editor: Javier Caceres
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
Footnotes
-
Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.080338.124.
- Received November 25, 2024.
- Accepted April 2, 2025.
This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
