The elav gene plays an essential role in the developing nervous system of Drosophila. The elav protein was cloned and characterized molecularly by the White lab a number of years ago. It was shown to be expressed specifically within the nervous system and selectively within neuronal nuclei. The Elav protein has a modular structure comprising 3 C-terminal RNA binding domain (RBD) motifs, a tethering sequence between the second and 3rd domain and an N-terminal auxiliary domain. Particular interest has centered on the RBD domains since they raise the intriguing notion that Elav may participate in the control of neuro-specific RNA biogenesis or stability. RBD domains in the Drosophila sex lethal protein play an important role in regulating sex-specific splicing in flies and several RBD-containing proteins in mammalian cells have been implicated in controlling RNA stability. Recent studies from the White lab provide strong evidence that the Elav protein is both necessary and sufficient for the neuron-specific splicing of the cell surface protein neuroglian. Although the phenomenon of neuron-specific splicing was first described over a decade ago no transacting neuron-specific factors have been identified. Elav represents an excellent candidate for a neuron-specific splicing factor. This proposal is designed to analyze the function of elav in neuron-specific splicing.
