PRIGLUE | Protein-RNA interaction stabilization using molecular glues

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101076498
Start date: 01-06-2023
End date: 31-05-2028
Total budget - Public funding: 1 500 000,00 Euro - 1 500 000,00 Euro
Cordis data

Original description

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.

Status

SIGNED

Call topic

ERC-2022-STG

Update Date

09-02-2023
Geographical location(s)
Structured mapping
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EU-Programme-Call
Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2022-STG ERC STARTING GRANTS
HORIZON.1.1.1 Frontier science
ERC-2022-STG ERC STARTING GRANTS