METTL3-mediated m⁶A is required for murine oocyte maturation and maternal-to-zygotic transition

Abstract

N⁶-methyladenosine (m⁶A) is the most prevalent epigenetic modification of messenger RNA (mRNA) in higher eukaryotes; this modification is mainly catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. Although m⁶A modification has been proven to play an essential role in diverse biological processes, our knowledge of <i>Mettl3</i> is still limited because <i>Mettl3</i> mutations are lethal to embryos in both mammals and plants. In this study, we knocked down <i>Mettl3</i> by microinjection of its specific short interfering RNAs (siRNAs) or morpholino into fully grown germinal vesicle (GV) oocytes. As a result, we demonstrated that knocking down <i>Mettl3</i> in female germ cells severely inhibited oocyte maturation by decreasing mRNA translation efficiency and led to defects in the maternal-to-zygotic transition, probably due to its interference in disrupting mRNA degradation. The discovery from this study suggests that the reversible m⁶A modification has vital functions in mammalian oocyte maturation and pre-implantation embryonic development processes.