Inosine RNA modifications are enriched at the codon wobble position in mouse oocytes and eggs

Abstract

Mammalian oocytes and eggs are transcriptionally quiescent and depend on post-transcriptional mechanisms for proper maturation. Post-transcriptional mRNA modifications comprise an important regulatory mechanism that can alter protein and miRNA recognition sites, splicing, stability, secondary structure, and protein coding. We discovered that fully grown mouse germinal vesicle oocytes and metaphase II eggs display abundant inosine mRNA modifications compared to growing oocytes from postnatal day 12 oocytes. These inosines were enriched in mRNA protein coding regions (CDS) and specifically located at the third codon base, or wobble position. Inosines, observed at lower frequencies in CDS of somatic tissues, were similarly enriched at the codon wobble position. In oocytes and eggs, inosine modifications lead primarily to synonymous changes in mRNA transcripts. Inosines may ultimately affect maternal mRNA stability by changing codon usage, thereby altering translational efficiency and translationally coupled mRNA degradation. These important observations advance our understanding of post-transcriptional mechanisms contributing to mammalian oocyte maturation.