ELAV mediates circular RNA biogenesis in neurons [RNA-seq, sm]

Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous system of animals, where they are thought to regulate gene expression and synaptic function. Here, we show that neuronal circRNA biosynthesis is mediated by the pan-neuronal RNA-binding protein ELAV. In Drosophila embryos, we characterize the circRNA landscape in normal and elav mutant neurons. We find that neuronal circRNAs are globally depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In fly brains, ELAV binds to pre-mRNA introns flanking putative circRNAs and decreases efficiency of linear splicing in favor of intron pairing at reverse complementary matches, inducing circularization. Together, our data demonstrate that ELAV directly modulates splicing decisions to generate the neuronal circRNA landscape. RNA-seq from sorted cells of Drosophila melanogaster embryos, aged 14 to 16h after egg laying : 3 replicates of non-neuronal cells sample, of wild-type neurons sample (mixed sex and female), and of Δelav mutant neurons sample respectively