N6-methyladenosine regulates maternal RNA maintenance in oocytes and timely RNA decay during mouse maternal-to-zygotic transition

• Published in: Nature cell biology Vol. 24; no. 6; pp. 917 - 927
• Main Authors: Wu, You, Xu, Xiaocui, Qi, Meijie, Chen, Chuan, Li, Mengying, Yan, Rushuang, Kou, Xiaochen, Zhao, Yanhong, Liu, Wenqiang, Li, Yanhe, Liu, Xuelian, Zhang, Meiling, Yi, Chengqi, Liu, Hongbin, Xiang, Junhong, Wang, Hong, Shen, Bin, Gao, Yawei, Gao, Shaorong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2022; Nature Publishing Group
• Subjects: 13; 13/100; 14/19; 38; 38/39; 38/89; 38/90; 38/91; 631/136/2086; 631/1647; 631/337/1645/2020; 631/337/1645/2570; 64/60; Biomedical and Life Sciences; Cancer Research; Cell Biology; Decay; Developmental Biology; Embryos; Fertilization; Gametocytes; Gene mapping; Gene sequencing; Genomes; Immunoprecipitation; Life Sciences; Methylation; Methyltransferase; N6-methyladenosine; Oocytes; Ribonucleic acid; RNA; Stability; Stem Cells; Transcriptomes
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/s41556-022-00915-x

N 6 -methyladenosine (m 6 A) and its regulatory components play critical roles in various developmental processes in mammals. However, the landscape and function of m 6 A in early embryos remain unclear owing to limited materials. Here we developed a method of ultralow-input m 6 A RNA immunoprecipitation followed by sequencing to reveal the transcriptome-wide m 6 A landscape in mouse oocytes and early embryos and found unique enrichment and dynamics of m 6 A RNA modifications on maternal and zygotic RNAs, including the transcripts of transposable elements MTA and MERVL. Notably, we found that the maternal protein KIAA1429, a component of the m 6 A methyltransferase complex, was essential for m 6 A deposition on maternal mRNAs that undergo decay after zygotic genome activation and MTA transcripts to maintain their stability in oocytes. Interestingly, m 6 A methyltransferases, especially METTL3, deposited m 6 A on mRNAs transcribed during zygotic genome activation and ensured their decay after the two-cell stage, including Zscan4 and MERVL. Together, our findings uncover the essential functions of m 6 A in specific contexts during the maternal-to-zygotic transition, namely ensuring the stability of mRNAs in oocytes and the decay of two-cell-specific transcripts after fertilization. Wu et al. optimized the m 6 A mapping method for ultralow-input materials and characterized the transcriptome-wide landscape of m 6 A methylation in mouse oocytes and early embryos.