RNA metabolism in developing neurons (360G-Wellcome-217213_Z_19_Z)

Understanding how neurons translate extracellular cues into specific patterns of gene expression is amongst the major goals of modern neurobiology. Efforts to unravel the molecular basis of localised gene expression have mostly focused on transcriptional control and mRNA transport. However, post- transcriptional mRNA processing is increasingly recognised as an essential step in the propagation of genetic information. Importantly, incorrect processing and delivery of mRNA causes developmental defects and severe human neurological disorders. The overarching scope of this project is to investigate novel mechanisms of mRNA metabolism that are likely to be conserved in all mammalian cells and to provide new insights regarding how gene expression is regulated in neurons. The 3’ untranslated regions (3’UTRs) of RNA transcripts play a key role in mediating many steps of RNA metabolism, including splicing, nuclear export and localization. We performed 3’end-Seq screens of transcripts localised in sub-cellular compartments of sympathetic neurons and are uniquely positioned to tackle the question of how 3’UTRs regulate RNA metabolism in neurons. We will address the following questions: - What determines the fate of a bifunctional mRNA? - Does the 3’UTR influence the proteome in sympathetic neurons? - Do 3’UTRs generate a new class of RNAs that regulate neuronal development?