TY - JOUR
T1 - Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals
AU - Torres-méndez, Antonio
AU - Pop, Sinziana
AU - Bonnal, Sophie
AU - Almudi, Isabel
AU - Avola, Alida
AU - Roberts, Ruairí J. V.
AU - Paolantoni, Chiara
AU - Alcaina-Caro, Ana
AU - Martín-Anduaga, Ane
AU - Haussmann, Irmgard U.
AU - Morin, Violeta
AU - Casares, Fernando
AU - Soller, Matthias
AU - Kadener, Sebastian
AU - Roignant, Jean-Yves
AU - Prieto-Godino, Lucia
AU - Irimia, Manuel
PY - 2022/1/28
Y1 - 2022/1/28
N2 - 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.
AB - 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.
U2 - 10.1126/sciadv.abk0445 1,048
DO - 10.1126/sciadv.abk0445 1,048
M3 - Article
SN - 2375-2548
VL - 8
JO - Science Advances
JF - Science Advances
IS - 4
M1 - eabk0445
ER -