A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons

Torres Méndez, Antonio; Bonnal, Sophie; Marquez, Yamile; Roth, Jonathan; Iglesias, Marta; Permanyer, Jon; Almudi, Isabel; O'Hanlon, Dave; Guitart, Tanit; Soller, Matthias; Gingras, Anne-Claude; Gebauer, Fátima; Rentzsch, Fabian; Blencowe, Benjamin J.; Valcárcel, J. (Juan); Irimia Martínez, Manuel

A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons

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dc.contributor.author Torres Méndez, Antonio
dc.contributor.author Bonnal, Sophie
dc.contributor.author Marquez, Yamile
dc.contributor.author Roth, Jonathan
dc.contributor.author Iglesias, Marta
dc.contributor.author Permanyer, Jon
dc.contributor.author Almudi, Isabel
dc.contributor.author O'Hanlon, Dave
dc.contributor.author Guitart, Tanit
dc.contributor.author Soller, Matthias
dc.contributor.author Gingras, Anne-Claude
dc.contributor.author Gebauer, Fátima
dc.contributor.author Rentzsch, Fabian
dc.contributor.author Blencowe, Benjamin J.
dc.contributor.author Valcárcel, J. (Juan)
dc.contributor.author Irimia Martínez, Manuel
dc.date.accessioned 2019-07-29T06:13:39Z
dc.date.issued 2019
dc.description.abstract The mechanisms by which entire programmes of gene regulation emerged during evolution are poorly understood. Neuronal microexons represent the most conserved class of alternative splicing in vertebrates, and are critical for proper brain development and function. Here, we discover neural microexon programmes in non-vertebrate species and trace their origin to bilaterian ancestors through the emergence of a previously uncharacterized 'enhancer of microexons' (eMIC) protein domain. The eMIC domain originated as an alternative, neural-enriched splice isoform of the pan-eukaryotic Srrm2/SRm300 splicing factor gene, and subsequently became fixed in the vertebrate and neuronal-specific splicing regulator Srrm4/nSR100 and its paralogue Srrm3. Remarkably, the eMIC domain is necessary and sufficient for microexon splicing, and functions by interacting with the earliest components required for exon recognition. The emergence of a novel domain with restricted expression in the nervous system thus resulted in the evolution of splicing programmes that qualitatively expanded the neuronal molecular complexity in bilaterians.
dc.description.sponsorship This work has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-StG-LS2-637591 to M.Ir. and ERC-AdvG-670146 to J.V.), the Spanish Ministry of Economy and Competitiveness (BFU2014-55076-P and BFU2017-89201-P to M.Ir., BFU2014-005153 to J.V., and the ‘Centro de Excelencia Severo Ochoa 2013–2017’ (SEV-2012-0208)), AGAUR, Fundación Botín (to J.V.) and the Canadian Institutes of Health Research (to B.J.B. and A.-C.G.). RNP mass spectrometric analyses were performed at the CRG/UPF Proteomics Unit (part of ProteoRed-PRB3, supported by PE I+D+i 2013–2016 (PT17/0019) of the ISCIII and ERDF) by ‘Programa CERCA Generalitat de Catalunya’ and ‘Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement’ (2017SGR595). A.T.-M. held an FPI-SO fellowship, and Y.M. a Marie Skłodowska-Curie individual fellowship.
dc.format.mimetype application/pdf
dc.identifier.citation Torres-Méndez A, Bonnal S, Marquez Y, Roth J, Iglesias M, Permanyer J et al. A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nat Ecol Evol. 2019;3(4):691-701. DOI: 10.1038/s41559-019-0813-6
dc.identifier.doi http://dx.doi.org/10.1038/s41559-019-0813-6
dc.identifier.issn 2397-334X
dc.identifier.uri http://hdl.handle.net/10230/42196
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nature Ecology and Evolution. 2019;3(4):691-701
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670146
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/637591
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55076-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89201-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-005153
dc.rights © Springer Nature Publishing AG Torres-Méndez A, Bonnal S, Marquez Y, Roth J, Iglesias M, Permanyer J, Almudí I, O'Hanlon D, Guitart T, Soller M, Gingras AC, Gebauer F, Rentzsch F, Blencowe BJ, Valcárcel J, Irimia M. A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nat Ecol Evol. 2019; 3(4):691-701 [http://dx.doi.org/10.1038/s41559-019-0813-6]
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword Comparative genomics
dc.subject.keyword Computational biology and bioinformatics
dc.subject.keyword Evolution
dc.subject.keyword Evolutionary developmental biology
dc.subject.keyword Evolutionary genetics
dc.title A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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