Deciphering neuronal RBP regulation of mRNA transport and translation in synaptic plasticity (360G-Wellcome-309570_Z_24_Z)

At brain synapses, the direct functional connection between neurons, RNA localization and local regulation of protein synthesis are critical components for sculpting the synaptic proteome. With thousands of mRNAs localized and translated in neuronal processes, understanding how the brain controls their successful transport to these distal sites and when they are made into protein is an outstanding question. At the crux of regulating RNA, from the moment it is transcribed to when it is degraded, is an ever-expanding list of RNA binding proteins (RBPs) whose association with RNA governs all aspects of RNA biology, including its transport and subsequent translation. Here, with both in vitro and in vivo approaches, my group will test the hypothesis that distinct plasticity states invoke unique translational programs, requiring the recruitment of mRNA and local protein synthesis at the synapse, modulated through the dynamic remodelling of the network of RNA binding proteins associated with mRNA. The insights gained from this work will enhance our understanding of how the brain regulates and adapts its synaptic proteome during plasticity and aid our efforts to understand the molecular underpinnings of neurological diseases resulting from the dysregulation of RBPs. Key terms: RNA, RNA binding proteins, local protein synthesis