Mettl14 is required for mouse post-implantation development by facilitating epiblast maturation

ABSTRACT N6-methyladenosine (m 6 A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m 6 A writer, reader, and eraser proteins. As an m 6 A writer, the METTL3–METTL14-WTAP complex dynamically regulates m 6 A modification and plays important roles in diverse biological processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation and their impacts on different biological pathways, are still very limited. Here, by employing both in vivo and in vitro models, we report that METTL14 was indispensable for post-implantation embryonic development by facilitating the conversion from naïve to primed state of the epiblast. Depletion of Mettl14 lead to conspicuous embryonic growth retardation from E6.5 mainly as a result of resistance to differentiation, which further lead to embryonic lethality early in gestation. Our data highlight the critical function of METTL14, as an m 6 A modification regulator, in orchestrating early mouse embryogenesis.