Critical roles of mRNA m6A modification and YTHDC2 expression for meiotic initiation and progression in female germ cells

Abstract

Meiotic entry and progression require dynamic regulation of germline gene expression. m⁶A on mRNAs and recognition by YTHDC2 has been known as post-transcriptional regulatory complex, but the roles of this regulator remain unclear for meiotic initiation and progression in female germ cells (FGCs). This study showed that m⁶A modification occurred mainly in FGCs rather than ovarian somatic cells (SOMAs), and m⁶A levels in FGCs increased significantly with meiotic initiation. m⁶A inhibition suppressed expression of the meiotic markers and affected the percent of FGCs at zygotene, pachytene and diplotene stage respectively. YTHDC2 expression also increased in the same pattern with m⁶A. Ythdc2 knockdown decreased the percent of STRA8-positive FGCs and altered the percent of FGCs at zygotene and pachytene stage respectively. Taken together, these results suggest that mRNA m⁶A modification and YTHDC2 expression are essential for meiotic initiation and progression in FGCs.

Keywords: Female germ cells; Meiotic initiation; N(6)-methyladenosine (m(6)A); YTHDC2.