The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians

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  • dc.contributor.author Spruce, Thomas
  • dc.contributor.author Plass Pórtulas, Mireya, 1982-
  • dc.contributor.author Gohr, André
  • dc.contributor.author Ray, Debashish
  • dc.contributor.author Martínez de Lagrán Cabredo, María
  • dc.contributor.author Rot, Gregor
  • dc.contributor.author Nóvoa, Ana
  • dc.contributor.author Burguera, Demián
  • dc.contributor.author Permanyer, Jon
  • dc.contributor.author Miret-Cuesta, Marta
  • dc.contributor.author Zheng, Hong
  • dc.contributor.author Swanson, Maurice S.
  • dc.contributor.author Morris, Quaid
  • dc.contributor.author Mallo, Moises
  • dc.contributor.author Dierssen, Mara
  • dc.contributor.author Hughes, Timothy R.
  • dc.contributor.author Pernaute, Barbara
  • dc.contributor.author Irimia Martínez, Manuel
  • dc.date.accessioned 2022-06-21T09:18:17Z
  • dc.date.available 2022-06-21T09:18:17Z
  • dc.date.issued 2022
  • dc.description.abstract Understanding the regulatory interactions that control gene expression during the development of novel tissues is a key goal of evolutionary developmental biology. Here, we show that Mbnl3 has undergone a striking process of evolutionary specialization in eutherian mammals resulting in the emergence of a novel placental function for the gene. Mbnl3 belongs to a family of RNA-binding proteins whose members regulate multiple aspects of RNA metabolism. We find that, in eutherians, while both Mbnl3 and its paralog Mbnl2 are strongly expressed in placenta, Mbnl3 expression has been lost from nonplacental tissues in association with the evolution of a novel promoter. Moreover, Mbnl3 has undergone accelerated protein sequence evolution leading to changes in its RNA-binding specificities and cellular localization. While Mbnl2 and Mbnl3 share partially redundant roles in regulating alternative splicing, polyadenylation site usage and, in turn, placenta maturation, Mbnl3 has also acquired novel biological functions. Specifically, Mbnl3 knockout (M3KO) alone results in increased placental growth associated with higher Myc expression. Furthermore, Mbnl3 loss increases fetal resource allocation during limiting conditions, suggesting that location of Mbnl3 on the X chromosome has led to its role in limiting placental growth, favoring the maternal side of the parental genetic conflict.
  • dc.description.sponsorship The research has been funded by the Spanish Ministerio de Ciencia (BFU2017-89201-P and PID2020-115040GB-I00 to M.I.), the ‘Centro de Excelencia Severo Ochoa 2013-2017’(SEV-2012-0208 to the Centre for Genomic Regulation), and the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° 608959 to T.S.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Spruce T, Plass M, Gohr A, Ray D, Martínez de Lagrán M, Rot G et al. The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians. PLoS Biol. 2022 Apr 27;20(4):e3001615. DOI:10.1371/journal.pbio.3001615
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pbio.3001615
  • dc.identifier.issn 1544-9173
  • dc.identifier.uri http://hdl.handle.net/10230/53555
  • dc.language.iso eng
  • dc.publisher Public Library of Science (PLoS)
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/608959
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89201-P
  • dc.rights © 2022 Thomas Spruce et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Expressió gènica
  • dc.subject.other Proteïnes
  • dc.subject.other Placenta
  • dc.subject.other Biologia del desenvolupament
  • dc.title The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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