Dueling Endogenous Viral-Like Sequences Control Synaptic Plasticity

The function of a large part of most genomes, generally called “junk DNA”, remains largely unknown. Much of this enigmatic DNA corresponds to transposons, which are considered genomic parasites. Here, we show the protein of the Ty1 retrotransposonCopiais enriched at theDrosophilaneuromuscular junction and is transported across synapses. Unexpectedly, disruptingCopiaexpression results in increases in both synapse development and structural synaptic plasticity. Plasticity is kept in balance asCopiaantagonizes theDrosophila Arc(activity-regulated cytoskeleton-associated protein) homolog, which is a transposon-derived gene. Our cryo-EM structure of theCopiacapsid shows a shell with large cargo capacity and leads to a hypothesis for mutual antagonism of Arc andCopiacapsid assembly. Our findings provide evidence that a fully functional transposon plays a role at synapses, suggesting that transposons and other types of ‘junk DNA’ are essential to developmental and cellular processes.