In most species that undergo sexual reproduction, early embryogenesis is dominated by maternal mRNAs and proteins. To ensure subsequent development, these macromolecules are degraded and zygotic transcription is activated during a highly conserved maternal-to-zygotic transition (MZT). Degradation of maternal mRNAs occurs before or during zygotic genome activation (ZGA) and is essential for normal embryonic development (Ramos et al., 2004; Semotok et al., 2005), but the underlying molecular mechanisms are poorly understood. Two recent studies (Liu et al., 2016; Yu et al., 2016) report that BTG4 (B-cell translocation gene 4) is required to degrade maternal mRNAs in mice, which significantly advance our limited understanding of this important process in mammals.