PCV - Programme interdiciplinaire en physique et chimie du vivant

Structured RNA as biomolecular triggers: structure, interactions and chemical targeting – TriggeRNA

Submission summary

Structured RNA are major actors of numerous biological processes such as mRNA splicing, protein translation, control of gene expression, replication of viruses, RNA processing , chromosome maintenance… In most documented cases, the corresponding biological processes include one or more essential steps during which the RNA undergoes structural rearrangements involving the modification of secondary or tertiary interactions, the binding of a ligand or a protein or the interaction with another RNA. These RNA structural changes are sometimes quite extensive and can thus be viewed as biomolecular triggers which ultimately act on cell function. The structural bases and driving forces for such rearrangements are in many cases poorly understood, but are nevertheless major scientific issues and also of great potential therapeutic interest : as a result of their key roles, these RNA are now considered as promising drug targets. The objective of this project is twofold : (i) Obtaining systematic structural and functional information in a number of model systems, including RNA:RNA rearrangement events, RNA:ligand interaction and RNA self-association and (ii) Setting up a general strategy for identifying and designing small chemical compounds which can interfere with these triggering events, using a fragment-based chemical approach. For this purpose we plan to devise innovative strategies for producing RNA in vivo, by a recombinant approach. We will design a new, fluorescence-based assay for monitoring RNA triggering events. In parallel, We will assemble a diverse library of novel « RNA-friendly chemical compounds ». This set-up will allow for the screening of compounds able to modulate conformational switching of RNA. Proof-of-concept of some of these steps has already been established through a productive collaboration between the two groups associated in this proposal.

Project coordination

Frédéric DARDEL (CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR PARIS A)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR PARIS A

Help of the ANR 280,000 euros
Beginning and duration of the scientific project: - 36 Months

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