The lncRNA Statera regulates synaptogenesis by repressing the retrotransposon copia in Drosophila

Abstract

Retrotransposons are mobile genetic elements that can impair genome integrity, and their insertions and dysregulation have been implicated in various diseases. However, growing evidence suggests that retrotransposons may play important physiological roles. At the Drosophila larval neuromuscular junction (NMJ), the ViSyToR (Viral Synaptic Transfer of RNA) pathway requires the active retrotransposon copia as a key negative regulator of synaptogenesis. Here, we identify a long non-coding RNA, Statera (Stae), as a regulator of copia, initially discovered through its physical association with the Copia protein. Stae is highly expressed in the central nervous system and body wall muscles of Drosophila larvae. CRISPR knockout or RNAi knockdown of Stae leads to a general decrease of bouton number at the NMJ, indicating its role in promoting synaptogenesis. Furthermore, copia is highly upregulated in Stae mutants, suggesting that Stae functions to repress copia. Mechanistically, Stae reduces copia RNA stability and limits copia DNA copy number. Additional knockdown of copia in motor neuron-specific Stae RNAi animals rescues the abnormal NMJ morphology. Together, our findings reveal an unexpected role for a long non-coding RNA in promoting synaptogenesis by repressing a retrotransposon.