PRIGLUE · Protein-RNA interaction stabilization using molecular glues

Protein-RNA interactions play a key role in cell biology and there are limited tools for specific modulation. In this project we will look for molecules that act as glues by stabilizing the interaction between an RNA-binding protein and a specific RNA sequence which we call PRIGLUEs. The aims are to explore key concepts of how to develop screening methods to identify such PRIGLUEs and to determine what type of chemical matter is suitable for this approach. These novel molecular glues will be evaluated for their RNA selectivity and the mode of interaction stabilization. The methods we will develop to identify PRIGLUEs can be applied to any protein-RNA interaction, and we will use them to modulate the process of mRNA splicing to prove the concept. The glues will be applied to stabilize mutant splicing factor – RNA pairs to recover lost affinity and correct disease-causing splicing outcomes. PRIGLUEs will be applicable as novel tools for RNA biology studies but can eventually also lead to therapeutics with an unexplored mode of action.