METTL3 improves the development of somatic cell nuclear transfer embryos through AURKB and H3S10ph in goats.

Developmental abnormalities are more common in somatic cell nuclear transfer (SCNT) embryos due to epigenetic barriers that occur during the maternal-to-zygotic transition (MZT). N6-methyladenosine (m6A) is an RNA epigenetic modification that plays a significant role in numerous biological processes. However, the relationship between m6A and SCNT embryonic development is largely unexplored. In the present study, we found that the low expression of m6A methyltransferase-like 3 (METTL3) was associated with developmental arrest before zygotic genome activation (ZGA) in goat SCNT embryos and that karyokinesis defects were evident during their development. Notably, we demonstrated that METTL3 overexpression rescued the karyokinesis abnormalities, enhanced embryonic development and elevated the blastocyst formation rate. Further experiments revealed that METTL3 could mitigate the defects of maternal mRNA degradation, enhance the translation of Aurora kinase B (AURKB) and increase the phosphorylation of serine 10 on histone H3 (H3S10ph) to ensure the normal karyokinesis in SCNT embryos before ZGA in goats. Overall, our study highlights the essential role of METTL3 in enhancing the development of goat SCNT embryos. These findings indicate that METTL3 is critical for optimal SCNT efficiency and advance our understanding of m6A's role in embryonic development.