Parallel evolution of a splicing program controlling neuronal excitability in flies and mammalsMore about Open Access at the Crick
Authors listAntonio Torres Mendez Sinzi Pop Sophie Bonnal Isabel Almudi Alida Avola Ruairi Roberts Chiara Paolantoni Ana Alcaina-Caro Ane Martín-Anduaga Irmgard U Haussmann Violeta Morin Fernando Casares Matthias Soller Sebastian Kadener Jean-Yves Roignant Lucia Prieto Godino Manuel Irimia
Alternative splicing increases neuronal transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. In nonvertebrate bilaterians, this splicing program is restricted to neurons by the posttranscriptional processing of the enhancer of microexons (eMIC) domain in Srrm234. In Drosophila, this processing is dependent on regulation by Elav/Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell type-specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. We found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient posttranscriptional programs can evolve independently in different phyla to affect distinct cellular modules while maintaining cell-type specificity.
Journal Science advances
Issue number 4