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

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  • dc.contributor.author Torres Méndez, Antonio, 1992-
  • dc.contributor.author Pop, Sinziana
  • dc.contributor.author Bonnal, Sophie
  • dc.contributor.author Almudi, Isabel
  • dc.contributor.author Avola, Alida
  • dc.contributor.author Roberts, Ruairí J. V.
  • dc.contributor.author Paolantoni, Chiara
  • dc.contributor.author Alcaina-Caro, Ana
  • dc.contributor.author Martín-Anduaga, Ane
  • dc.contributor.author Haussmann, Irmgard U.
  • dc.contributor.author Morin, Violeta
  • dc.contributor.author Casares, Fernando
  • dc.contributor.author Soller, Matthias
  • dc.contributor.author Kadener, Sebastian
  • dc.contributor.author Roignant, Jean-Yves
  • dc.contributor.author Prieto-Godino, Lucia
  • dc.contributor.author Irimia Martínez, Manuel
  • dc.date.accessioned 2022-06-13T08:55:52Z
  • dc.date.available 2022-06-13T08:55:52Z
  • dc.date.issued 2022
  • dc.description.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.
  • dc.description.sponsorship The research has been funded by the following: European Research Council ERC-StG-LS2-637591 (M.I.), European Research Council ERC-CoG-LS2-101002275 (M.I.), European Research Council ERC StG “EvoNeuroCircuit” 802531 (L.P.-G.), Spanish Ministerio de Ciencia BFU2017-89201-P (M.I.), NIH R01 grant R01GM122406 (S.K.), BBSRC (M.S.), Centro de Excelencia Severo Ochoa 2013-2017 SEV-2012-0208 (CRG), Cancer Research UK FC001594 (Francis Crick Institute), U.K. Medical Research Council FC001594 (Francis Crick Institute), Wellcome Trust FC001594 (Francis Crick Institute), FPI-Severo Ochoa PhD fellowship (A.T.-M.), Boehringer Ingelheim Fonds travel grant (A.T.-M.), and Boehringer Ingelheim Fonds PhD fellowship (R.J.V.R.)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Torres-Méndez A, Pop S, Bonnal S, Almudi I, Avola A, Roberts RJV et al. Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals. Sci Adv. 2022 Jan 28;8(4):eabk0445. DOI:10.1126/sciadv.abk0445
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abk0445
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/53471
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/637591
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/802531
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101002275
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89201-P
  • dc.rights © 2022 Antonio Torres-Méndez et al, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY)
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Genòmica
  • dc.subject.other Neurologia
  • dc.title Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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