The Francis Crick Institute
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Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals.

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journal contribution
posted on 2022-02-03, 11:49 authored by Antonio Torres-Méndez, Sinziana Pop, Sophie Bonnal, Isabel Almudi, Alida Avola, Ruairí JV 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.


Crick (Grant ID: 10594, Grant title: Godino FC001594) European Research Council (Grant ID: 802531 - EvolutioNeuroCircuit, Grant title: ERC 802531 - EvolutioNeuroCircuit)