Nova Mediates Experience Dependent Processing of Orb2A mRNA

Abstract

Memory serves the vital function of associating disparate stimuli to modify future behavior for fitness. For instance, Drosophila melanogaster can learn to associate neutral odors with sweet metabolically available sugars and remember this association for days. Memory formation is thought to rely on stable changes in synaptic strength dictated by the internal state of the organism and the nature of the external stimuli it encounters. In flies, long-term memory requires the efficient oligomerization of the translation regulator Orb2, a process that is dependent on the protein isoform Orb2A. The mechanisms that regulate Orb2A protein levels will therefore determine which experiences become lasting memories. Here we show that Orb2A mRNA exists in a non-protein coding form in the brain via intron retention. Upon exposure to external stimuli sufficient to induce long-term memory, the amount of protein coding Orb2A mRNA increases. Furthermore, the protein coding form of Orb2A mRNA requires the Drosophila homologue of Nova-1/2, a well characterized mammalian nervous system specific alternative splicing factor. Our results implicate mRNA processing as a regulatory step in memory formation via the Nova dependent maturation of Orb2A mRNA.