RNA-scaffolded RNP condensation, its physiologic regulation, and therapeutic modulation
Year of award: 2019
Grantholders
Prof Jernej Ule
King's College London
Project summary
Protein-RNA complexes play key roles in controlling gene expression. In neurons, many RNA molecules travel to the long extensions formed by neurons, called axons or dendrites, where they enable gene expression to be regulated in response to local stimuli, which contributes to formation of memories and to regeneration of neurons. Mutations that initiate diseases such as amyotrophic lateral sclerosis (ALS) often disrupt the regulation of these localised RNAs. We will study the unique properties of protein-RNA complexes that assemble on the localised RNAs by using high-throughput technologies, with a focus on the role of RNA structures. We will establish new experimental and computational methods to gain insights into the roles these structures play in healthy and diseased neurons. Thereby, we aim to develop new therapeutic approaches that could neutralise the effects of genetic mutations in ALS, in order to re-establish the appropriate regulation of neuronal RNAs.