Fig. 5: METTL3-mediated m⁶A regulates RNA stability to affect oocyte maturation.

A Volcano plot showing the expression differences for target transcripts under Mettl3^Gdf9 cKO. Transcripts with average RPKM values >3 in WT, |log₂ fold change| values > log₂ (1.2), and p values <0.05 as determined by DESeq2 were regarded as significantly dysregulated transcripts. The numbers of significantly downregulated (blue) and upregulated (red) transcripts are shown. The vertical dashed lines indicate the cutoff of |log₂ fold change| = |log₂ (1.2)|, and the horizontal dashed lines indicate the cutoff of p = 0.05. B Bar plot showing the ratios of transcripts with m⁶A modification among downregulated transcripts and upregulated transcripts under Mettl3 knockout. C Bar plot showing the expression of Igf2bp1, Igf2bp2, and Igf2bp3 in GV oocytes, as determined by RNA-seq in this study and in the GSE96638 dataset. The data were shown as the mean ± SEM of two independent experiments for this study and 26 independent experiments for the GSE96638 dataset. D Density plot showing the distance between IGF2BP2/3 peaks identified by eCLIP (GSE78509) in hESCs and m⁶A peaks identified by MeRIP-seq in this study. The background was obtained by randomly shuffling IGF2BP peaks using BEDTools’ shuffleBed tool. The p value was determined by the two-sided Kolmogorov–Smirnov test. E Venn diagram showing the overlay between downregulated expressed transcripts with m⁶A peaks and IGF2BP2/3 target transcripts. F Heatmap displaying the transcript abundance in WT and Mettl3^Gdf9 cKO oocytes. Transcripts with m⁶A modifications targeted by IGF2BPs are labeled brown, transcripts involved in meiosis or DNA repair are labeled in green or white, and the expression correlation between transcripts and Mettl3 is shown in red.