Mechanisms of axonal RNA transport

The objective of this study is to determine how the capacity for localized protein synthesis in axons is altered by injury. In the peripheral nervous system, localized protein synthesis can be triggered by axotomy and lack of capacity for localized protein synthesis may contribute to failed regeneration of axons in the central nervous system (CNS). Here we are focusing on the role of RNA binding proteins (RBPs) in delivering mRNAs into axons.  From ongoing studies in our and other labs, it is now obvious that transport of mRNAs is regulated by both exogenous and endogenous mechanisms. We hope to determine whether injury changes the capacity for localization of axonal mRNAs through altered expression or altered activity of its RBPs. These studies will provide a unique molecular view of how the capability for axonal mRNA localization and localized translation contributes to axonal regeneration. These studies are 2 pronged. First, to identify the axonal RNA localization elements within the 3’UTR using conserved sequence and structural motif bioinformatic analyses. Second, to identify the proteins that bind to these cis elements, and test whether injury alters their levels or the ability to interact with their target mRNAs.