Dysregulation of the networking of RNA-binding proteins (RBPs) and RNAs drives many human diseases, including cancers, and the targeting of RNA–protein interactions (RPIs) has emerged as an exciting area of RNA-targeted drug discovery.Dysregulation of the networking of RNA-binding proteins (RBPs) and RNAs drives many human diseases, including cancers, and the targeting of RNA–protein interactions (RPIs) has emerged as an exciting area of RNA-targeted drug discovery. Accordingly, methods that enable the discovery of cell-active small molecule modulators of RPIs are needed to propel this emerging field forward. Herein, we describe the application of live-cell assay technology, RNA interaction with protein-mediated complementation assay (RiPCA), for high-throughput screening to identify small molecule inhibitors of the pre-let-7d–Lin28A RPI. Utilizing a combination of RNA-biased small molecules and virtual screening hits, we discovered an RNA-binding small molecule that can disrupt the pre-let-7–Lin28 interaction demonstrating the potential of RiPCA for advancing RPI-targeted drug discovery.
CITATION STYLE
Rosenblum, S. L., Soueid, D. M., Giambasu, G., Vander Roest, S., Pasternak, A., DiMauro, E. F., … Garner, A. L. (2024). Live cell screening to identify RNA-binding small molecule inhibitors of the pre-let-7–Lin28 RNA–protein interaction. RSC Medicinal Chemistry. https://doi.org/10.1039/d4md00123k
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