Long Noncoding RNA SDRG Regulates Drosophila Neuromuscular Synapse Development by Modulating Frequenin 2 Through Coracle

Synapses are specialized structures for information exchange between neurons and their targets, and precise regulation of synaptic growth is crucial for the formation and plasticity of neural circuits. The neuromuscular junction (NMJ) of fruit fly larvae is an excellent model for studying molecular mechanisms underlying synaptic development. There are few reports on the role of long noncoding RNAs (lncRNAs) in synaptic development at NMJ. Here, we reported a lncRNA, Synapse Development Regulatory Gene (SDRG), which regulates synaptic growth by antagonizing frequenin 2 (frq2) through Coracle (Cora). SDRG deficiency induced synaptic overgrowth characterized by excess satellite boutons at NMJ terminals, and simultaneously high frequenin 1 (frq1) and frq2 RNA levels. Genetically, frq2, not frq1, knock-down driven by motoneuron-specific Gal4 could rescue this growth defect, which was mediated by Cora protein. At the molecular level, SDRG promotes the recruitment of Cora protein to frq2 RNA. Our work exhibits a new function of lncRNA and is beneficial for unveiling the pathogenesis of neuropsychiatric disorders with abnormal synaptic development.