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Spruce, Thomas; Plass, Mireya; Gohr, André; Ray, Debashish; Martínez de Lagrán, María; Rot, Gregor; Nóvoa, Ana; Burguera, Demian; Permanyer, Jon; Miret, Marta; Zheng, Hong; Swanson, Maurice S.; Morris, Quaid; Mallo, Moises; Dierssen, Mara; Hughes, Timothy R.; Pernaute, Barbara; Irimia, Manuel

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

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  • Media type: E-Article
  • Title: The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians
  • Contributor: Spruce, Thomas; Plass, Mireya; Gohr, André; Ray, Debashish; Martínez de Lagrán, María; Rot, Gregor; Nóvoa, Ana; Burguera, Demian; Permanyer, Jon; Miret, Marta; Zheng, Hong; Swanson, Maurice S.; Morris, Quaid; Mallo, Moises; Dierssen, Mara; Hughes, Timothy R.; Pernaute, Barbara; Irimia, Manuel
  • imprint: Public Library of Science (PLoS), 2022
  • Published in: PLOS Biology
  • Language: English
  • DOI: 10.1371/journal.pbio.3001615
  • ISSN: 1545-7885
  • Keywords: General Agricultural and Biological Sciences ; General Immunology and Microbiology ; General Biochemistry, Genetics and Molecular Biology ; General Neuroscience
  • Origination:
  • Footnote:
  • Description: <jats:p>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<jats:italic>Mbnl3</jats:italic>has undergone a striking process of evolutionary specialization in eutherian mammals resulting in the emergence of a novel placental function for the gene.<jats:italic>Mbnl3</jats:italic>belongs to a family of RNA-binding proteins whose members regulate multiple aspects of RNA metabolism. We find that, in eutherians, while both<jats:italic>Mbnl3</jats:italic>and its paralog<jats:italic>Mbnl2</jats:italic>are strongly expressed in placenta,<jats:italic>Mbnl3</jats:italic>expression has been lost from nonplacental tissues in association with the evolution of a novel promoter. Moreover,<jats:italic>Mbnl3</jats:italic>has undergone accelerated protein sequence evolution leading to changes in its RNA-binding specificities and cellular localization. While<jats:italic>Mbnl2</jats:italic>and<jats:italic>Mbnl3</jats:italic>share partially redundant roles in regulating alternative splicing, polyadenylation site usage and, in turn, placenta maturation,<jats:italic>Mbnl3</jats:italic>has also acquired novel biological functions. Specifically,<jats:italic>Mbnl3</jats:italic>knockout (M3KO) alone results in increased placental growth associated with higher<jats:italic>Myc</jats:italic>expression. Furthermore,<jats:italic>Mbnl3</jats:italic>loss increases fetal resource allocation during limiting conditions, suggesting that location of<jats:italic>Mbnl3</jats:italic>on the X chromosome has led to its role in limiting placental growth, favoring the maternal side of the parental genetic conflict.</jats:p>
  • Access State: Open Access