Open AccessParallel evolution of a splicing program controlling neuronal excitability in flies and mammals
Author(s) -
Antonio Torres-Méndez,
Sînziana Pop,
Sophie Bonnal,
Isabel Almudí,
Alida Avola,
Ruairí J.V. Roberts,
Chiara Paolantoni,
Ana AlcainaCaro,
Ane Martín Anduaga,
Irmgard U. Haussmann,
Violeta Morín,
Fernando Casares,
Matthias Soller,
Sebastián Kadener,
JeanYves Roignant,
Lucía L. Prieto-Godino,
Manuel Irimia
Publication year - 2022
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abk0445
Subject(s) - biology , alternative splicing , exon , rna splicing , enhancer , transcriptome , drosophila (subgenus) , genome , evolutionary biology , genetics , neuroscience , gene , gene expression , rna
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 inDrosophila and compared it with that of mammals. In nonvertebrate bilaterians, this splicing program is restricted to neurons by the posttranscriptional processing of theenhancer of microexons (eMIC) domain inSrrm234 . InDrosophila , 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.