RNA-methyltransferase Nsun5 controls the Maternal-to-Zygotic Transition by regulating Maternal mRNA stability

Here, we show that deletion of the m5C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m5C revealed that the level of m5C decreased in a time-dependent manner after Nsun5 knockout. Regarding maternal mRNA stability, we found that Nsun5 deficiency caused an m5C decline in the exon regions that influenced the translation efficiency of MAD2L2 and GDF9 in the ovary. Mechanistic investigations indicated that Nsun5 triggers aberrant alternative splicing events in the exon region of BRD8. Nsun5 loss arrests genesis and development in oocytes, indicating that Nsun5/m5C-regulated maternal mRNA stabilization is essential for maternal-to-zygotic transition.