RIVAgE: Roles and functional implications of the m6A pathway in the Pacific Oyster Magallana gigas within an Eco-Evo-Devo framework
m⁶A-epitranscriptomic regulation represents a mode of control of gene expression which, similarly to epigenetic regulation, modulates gene expression without altering the nucleotide sequence itself. m⁶A marks can be deposited on various types of transcripts at consensus sequences known as DRACH motifs. In Mammals, the m⁶A pathway participates in numerous processes at multiple levels: at the molecular scale, it regulates RNA splicing, degradation, and export; at a broader biological scale, these regulations impact embryonic development, cell differentiation, the maternal-to-zygotic transition, as well as neurogenesis and several neuronal processes such as memory formation and synaptic plasticity. The study of epitranscriptomic regulation constitutes a relatively recent research field (emerging in the early 2010s) and has been mainly explored in mammalian models. Nevertheless, functional roles of the m⁶A pathway have also been demonstrated in more distantly related species belonging to all major bilaterian lineages, with the notable exception of Lophotrochozoans — despite their highly conserved enzymatic machinery. In this work, we used the lophotrochozoan model Magallana gigas to investigate the functional roles of m⁶A regulation in several biological contexts: during embryonic development, in the context of chromatin dosage compensation in triploid adult oysters, and finally in an evolutionary perspective, by exploring the conservation of the m⁶A pathway across the bilaterian lineage. These complementary approaches revealed a strong conservation of the functional roles of the epitranscriptomic pathway in this lophotrochozoan model, notably in embryonic development, splicing regulation, nervous system establishment, and carRNA-dependent mechanisms involved in chromatin dosage compensation. They also suggest the existence of a crosstalk between epigenetic and epitranscriptomic regulations, which is likely conserved throughout bilaterian evolution. Thus, our results converge toward the idea that m⁶A plays a central role in developmental and evolutionary processes, as part of an integrative eco-evo-devo perspective.
Thesis jury :
- Céline Cosseau (University Professor, University of Perpignan Via Domitia), Rapporteur
- Hervé Le Hir (Research Director, ENS – CNRS), Rapporteur
- Elodie Fleury (Research Associate, Ifremer), Examiner
- Eve Gazave (Research Director, Institut Jacques Monod), Examiner
- Pascal Favrel (University Professor, University of Caen Normandie), Examiner
- Guillaume Rivière ( University Professor, University of Caen Normandie),Thesis Director