Alfonso-Gonzalez Carlos, Shi Mengjin, Gorey Sakshi, Holec Sarah, Carrasco Judit, Rauer Michael, Tsagkris Stylianos, Mateos Fernando, Hilgers Valérie
Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany;
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Genes Dev. 2025 Sep 2;39(17-18):1064-1080. doi: 10.1101/gad.352670.125.
Circular RNAs (circRNAs) arise from back-splicing of precursor RNAs and accumulate in the nervous systems 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 embryos, we characterized the circRNA landscape in normal and mutant neurons. We found that neuronal circRNAs are globally (>75%) depleted upon ELAV knockout, and induction of ELAV expression drives ectopic RNA circularization. In brain tissue, 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.
环状RNA（circRNAs）由前体RNA的反向剪接产生，并在动物的神经系统中积累，人们认为它们在其中调节基因表达和突触功能。在这里，我们表明神经元circRNA的生物合成由泛神经元RNA结合蛋白ELAV介导。在胚胎中，我们对正常和突变神经元中的circRNA图谱进行了表征。我们发现，ELAV基因敲除后，神经元circRNAs整体（>75%）减少，而ELAV表达的诱导驱动异位RNA环化。在脑组织中，ELAV与假定circRNAs侧翼的前体mRNA内含子结合，并降低线性剪接效率，有利于反向互补匹配处的内含子配对，从而诱导环化。总之，我们的数据表明ELAV直接调节剪接决定以产生神经元circRNA图谱。
