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

Thomas Spruce, Mireya Plass, André Gohr, Debashish Ray, María Martínez de Lagrán, Gregor Rot, Ana Nóvoa, Demian Burguera, Jon Permanyer, Marta Miret, Hong Zheng, View ORCID ProfileMaurice S. Swanson, Quaid Morris, View ORCID ProfileMoises Mallo, View ORCID ProfileMara Dierssen, View ORCID ProfileTimothy R. Hughes, Barbara Pernaute, View ORCID ProfileManuel Irimia
doi: https://doi.org/10.1101/2021.09.08.459166
Thomas Spruce
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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  • For correspondence: thomas.spruce@crg.eu barbara.pernaute@crg.eu mirimia@gmail.com
Mireya Plass
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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André Gohr
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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Debashish Ray
2Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
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María Martínez de Lagrán
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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Gregor Rot
3Institute of Molecular Life Sciences of the University of Zurich and Swiss Institute of Bioinformatics, 8057 Zurich, Switzerland
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Ana Nóvoa
4Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal
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Demian Burguera
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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Jon Permanyer
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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Marta Miret
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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Hong Zheng
2Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
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Maurice S. Swanson
5Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
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  • ORCID record for Maurice S. Swanson
Quaid Morris
2Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
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Moises Mallo
4Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal
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Mara Dierssen
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
7Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain
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Timothy R. Hughes
2Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
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  • ORCID record for Timothy R. Hughes
Barbara Pernaute
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
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  • For correspondence: thomas.spruce@crg.eu barbara.pernaute@crg.eu mirimia@gmail.com
Manuel Irimia
1Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain
6Universitat Pompeu Fabra, Barcelona, Spain
8ICREA, Barcelona, Spain
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  • ORCID record for Manuel Irimia
  • For correspondence: thomas.spruce@crg.eu barbara.pernaute@crg.eu mirimia@gmail.com
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Abstract

The eutherian placenta is a major site for parental genetic conflict. Here, we identify the X-linked Mbnl3 gene as a novel player in this dispute. Mbnl3 belongs to an RNA binding protein family whose members regulate alternative splicing and other aspects of RNA metabolism in association with cellular differentiation. We find that, in eutherians, Mbnl3 has become specifically expressed in placenta and has undergone accelerated sequence evolution leading to changes in its RNA binding specificities. Although its molecular roles are partly redundant with those of Mbnl2, Mbnl3 has also acquired novel biological functions. In particular, whereas Mbnl2;Mbnl3 double knockout mice display severe placental maturation defects leading to strong histological and functional abnormalities, Mbnl3 knockout alone results in increased placental growth and favors placental and fetal resource allocation during limiting conditions.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians
Thomas Spruce, Mireya Plass, André Gohr, Debashish Ray, María Martínez de Lagrán, Gregor Rot, Ana Nóvoa, Demian Burguera, Jon Permanyer, Marta Miret, Hong Zheng, Maurice S. Swanson, Quaid Morris, Moises Mallo, Mara Dierssen, Timothy R. Hughes, Barbara Pernaute, Manuel Irimia
bioRxiv 2021.09.08.459166; doi: https://doi.org/10.1101/2021.09.08.459166
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The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians
Thomas Spruce, Mireya Plass, André Gohr, Debashish Ray, María Martínez de Lagrán, Gregor Rot, Ana Nóvoa, Demian Burguera, Jon Permanyer, Marta Miret, Hong Zheng, Maurice S. Swanson, Quaid Morris, Moises Mallo, Mara Dierssen, Timothy R. Hughes, Barbara Pernaute, Manuel Irimia
bioRxiv 2021.09.08.459166; doi: https://doi.org/10.1101/2021.09.08.459166

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