Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals

Torres-Méndez, Antonio and Manuel, Irimia and Haussmann, Irmgard U. and Soller, Matthias (2022) Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals. Science Advances, 8 (4). ISSN 2375-2548

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Abstract

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.

Item Type: Article
Identification Number: https://doi.org/10.1126/sciadv.abk0445
Dates:
DateEvent
8 December 2021Accepted
28 January 2022Published Online
Subjects: CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-01 - biosciences (non-specific)
CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-08 - molecular biology, biophysics and biochemistry
CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-10 - others in biosciences
Divisions: Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Irmgard Haussmann
Date Deposited: 30 Mar 2022 12:41
Last Modified: 30 Mar 2022 12:41
URI: http://www.open-access.bcu.ac.uk/id/eprint/13006

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