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ELAV Protein Governs Neural Circular RNA Production

Slowing linear splicing to favor back-splicing in fruit fly neurons reveals a mechanism for circular RNA formation that may operate in the human brain

Overview

  • Removing ELAV from Drosophila embryos reduces neuronal circular RNA levels by over 75%, while ectopic ELAV expression triggers new circRNA production in cells that normally produce few
  • ELAV binds to pre-mRNA introns flanking backsplice junctions, slowing conventional splicing and bringing splice sites into proximity to drive circRNA biogenesis
  • The closed-loop structure of circRNAs grants them extreme stability, making them long-lasting regulators of gene expression, synaptic function and neuronal development
  • Proteins similar to ELAV are conserved from flies to humans, suggesting this splicing-switch mechanism underlies circRNA landscapes across animal nervous systems
  • Targeting ELAV or its human analogs could enable modulation of circRNA levels, offering new strategies to study brain health and tackle neurodegenerative disorders