A functional m 6 A‐RNA methylation pathway in the oyster Crassostrea gigas assumes epitranscriptomic regulation of lophotrochozoan development

• Published in: The FEBS Journal
• Main Authors: Le Franc, Lorane, Bernay, Benoit, Petton, Bruno, Since, Marc, Favrel, Pascal, Rivière, Guillaume
• Other Authors: Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2020
• Subjects: development; epitranscriptomics; methylation; oyster; RNA; acl; [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology; [SDV.BDD]Life Sciences [q-bio]/Development Biology; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Genomics [q-bio.GN]; [SDE.BE]Environmental Sciences/Biodiversity and Ecology; Crassostrea gigas
• Online Access: https://hal.sorbonne-universite.fr/hal-02952460; https://hal.sorbonne-universite.fr/hal-02952460/document; https://hal.sorbonne-universite.fr/hal-02952460/file/Franc%20et%20al.%20-%20A%20functional%20m6A-RNA%20methylation%20pathway%20in%20the%20oy.pdf; https://doi.org/10.1111/febs.15500

International audience N6‐methyladenosine (m6A) is a prevalent epitranscriptomic mark in eukaryotic RNA, with crucial roles for mammalian and ecdysozoan development. Indeed, m6A‐RNA and the related protein machinery are important for splicing, translation, maternal‐to‐zygotic transition and cell differentiation. However, to date, the presence of an m6A‐RNA pathway remains unknown in more distant animals, questioning the evolution and significance of the epitranscriptomic regulation. Therefore, we investigated the m6A‐RNA pathway in the oyster Crassostrea gigas, a lophotrochozoan model whose development was demonstrated under strong epigenetic influence. Using mass spectrometry and dot blot assays, we demonstrated that m6A‐RNA is actually present in the oyster and displays variations throughout early oyster development, with the lowest levels at the end of cleavage. In parallel, by in silico analyses, we were able to characterize at the molecular level a complete and conserved putative m6A machinery. The expression levels of the identified putative m6A writers, erasers and readers were strongly regulated across oyster development. Finally, RNA pull‐down coupled to LC‐MS/MS allowed us to prove the actual presence of readers able to bind m6A‐RNA and exhibiting specific developmental patterns. Altogether, our results demonstrate the conservation of a complete m6A‐RNA pathway in the oyster and strongly suggest its implication in early developmental processes including MZT. This first demonstration and characterization of an epitranscriptomic regulation in a lophotrochozoan model, potentially involved in the embryogenesis, bring new insights into our understanding of developmental epigenetic processes and their evolution.