An important question of modern neurobiology is how neurons regulate synaptic response to excitation. Alternative pre-mRNA splicing and mRNA translation regulation in this response are two such examples of poorly understood mechanisms. We are studying the RNA-binding proteins (RBPs) that control these post-transcriptional processes using UV crosslinking-based purification method (CLIP) followed by high-throughput sequencing. Computational analysis of the resulting sequencing reads is used to define the sequence and structural features of RNA motifs recognized and bound by each RBP.

By integrating the biochemical and functional data, we are relating the position of RNA motifs to the activity of bound RBPs and predicting the central RNA-protein interactions in the regulatory network. We will test the physiological role of these core protein-RNA interactions using antisense RNAs.

The project aims to provide insights into the regulatory mechanisms underlying neuronal activity-dependent changes and to provide new opportunities for future treatments of neurodegenerative disorders. FRIs role is complete bioinformatics support and the development of new methods and tools for the analysis of CLIP high-throughput sequencing data and all derived analyses needed to gain an understanding of the mechanisms of protein-RNA interaction and regulation of transcription and translation.

To learn more about the project, you can visit the ERC (European Research Council; http://erc.europa.eu/index.cfm?fuseaction=page.display&topicID=224), or the Laboratory of Molecular Biology at the Medical Research Council (http://www2.mrc-lmb.cam.ac.uk/groups/jule/Ule_Lab_Homepage.html), web site.