Marking the transition

Nature 542, 475–478 (2017)

N⁶-Methyladenosine (m⁶A) is an mRNA post-translational modification that is recognized by the RNA-binding protein YTHDF2, which regulates mRNA stability. In order to understand the dynamics of m⁶A modification during embryonic development, Zhao et al. performed m⁶A sequencing of zebrafish maternal transcripts and found that 36% were m⁶A modified. Given that these maternal transcripts decreased in abundance during the maternal–zygotic transition (MZT), with a corresponding increase in zygotic transcription, the authors hypothesized that YTHDF2 might be involved in maternal mRNA clearance. Injection of GFP-labeled mRNA with and without the m⁶A modification into maternal ythdf2 zebrafish mutants revealed that m⁶A-modified RNA exhibited a slower rate of degradation during the MZT in these mutants relative to wild-type embryos. Consistent with this result, maternal ythdf2 zebrafish mutants exhibited an upregulation of maternal transcripts involved in cell cycle and reproduction and lowered levels of zygotic transcripts along with developmental delay and cell cycle progression defects, indicative of a defective MZT. Overall, these findings indicate that the m⁶A modification has a key role in transcriptome switching during early embryo development.