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Protein-RNA interaction stabilization using molecular glues

Project description

Molecular glues in protein-RNA interactions

Proteins interact with nucleic acids during key cellular processes such as DNA replication and transcription, RNA splicing and translation. These interactions are driven by the nucleotide sequence as well as the RNA-binding domains of the proteins. Funded by the European Research Council, the PRIGLUE project aims to identify molecules that act as glues to assist the interaction between RNA-binding proteins and RNA sequences. The methodology generated will help researchers investigate the chemistry and mode of action of such molecules and how they can be employed to restore the lost affinity of disease-related RNA-binding proteins. The work will advance the field of RNA biology and pave the way towards the design of innovative therapeutics.

Objective

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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(opens in new window) ERC-2022-STG

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Host institution

UNIVERSITAET MUENSTER
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 958 437,50
Address
SCHLOSSPLATZ 2
48149 Muenster
Germany

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Region
Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 958 437,50

Beneficiaries (2)

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