Title

Multiplexed dendritic targeting of RNAs by the A2 pathway in hippocampal neurons

Date of Completion

January 2008

Keywords

Biology, Neuroscience|Biology, Cell

Degree

Ph.D.

Abstract

In neurons, multiple RNAs are targeted to dendrites. Targeting and local translation of these RNAs is an important mechanism for cytoplasmic gene regulation that modulates synaptic plasticity. It is not known if different dendritically targeted RNAs are localized current knowledge about RNA localization in various systems. The second chapter provides evidence that multiple functionally coherent RNAs (CaMKII, NG and ARC) are localized to dendrites via the heteregenous ribonucleoprotein A2 (hnRNPA2) pathway. A common cis acting element present in these RNAs, called the hnRNPA2 response element (A2RE), interacts with trans acting factor, hnRNPA2 to mediate dendritic targeting. Experiments outlined in the third chapter show that tumor-overexpressed gene (TOG) is a multivalent ligand for hnRNPA2. TOG provides a scaffold for coassembling multiple hnRNPA2 molecules bound to RNA into composite RNA granules. The final step in dendritic RNA targeting is local translation. The fourth chapter describes a novel single molecule assay to measure dendritic translation of RNAs with spatial, temporal and molecular resolution. In the last chapter, we describe the multiplexing hypothesis for dendritic targeting. In multiplexing different dendritically localized RNA are packaged into a composite transport intermediate. Finally, we describe several human that may be caused by perturbing multiplexing. ^