ELAV mediates circular RNA biogenesis in neurons [RIP-seq]

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. Overall design: RNA Immunoprecipitation and sequencing (RIP-seq) of fruit fly heads. 2 different RIP experiments : one with FLAG antibody on elavFLAG flies (4 input samples and 4 IP samples), one with ELAV antibody on wild-type flies (3 input samples and 3 IP samples). The control samples are IP with FLAG antibody on wild-type flies (3 samples for input, 3 for IP).