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 retrotransposon Copia is enriched at the Drosophila neuromuscular junction and is transported across synapses. Unexpectedly, disrupting Copia expression results in increases in both synapse development and structural synaptic plasticity. Plasticity is kept in balance as Copia antagonizes the Drosophila Arc (activity-regulated cytoskeleton-associated protein) homolog, which is a transposon-derived gene. Our cryo-EM structure of the Copia capsid shows a shell with large cargo capacity and leads to a hypothesis for mutual antagonism of Arc and Copia capsid 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.