. 2022 Jun;24(6):917-927.

doi: 10.1038/s41556-022-00915-x. Epub 2022 May 23.

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

You Wu^#^{1

2

3}, Xiaocui Xu^#^{2

4}, Meijie Qi^#^{5

6}, Chuan Chen^{1

7}, Mengying Li⁵, Rushuang Yan¹, Xiaochen Kou⁴, Yanhong Zhao⁴, Wenqiang Liu⁴, Yanhe Li⁴, Xuelian Liu¹, Meiling Zhang⁸, Chengqi Yi⁸, Hongbin Liu⁹, Junhong Xiang^{10

11}, Hong Wang⁴, Bin Shen¹², Yawei Gao^{13

14

15}, Shaorong Gao^{16

17

18

19}

Affiliations

¹ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
² Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
³ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China.
⁴ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁵ State Key Laboratory of Reproductive Medicine, Center for Global Health, Gusu School, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
⁶ Center for Reproductive Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
⁷ Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁸ State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
⁹ Center for Reproductive Medicine, Cheeloo College of Medicine, Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
¹⁰ Department of Chemistry, The University of Chicago, Chicago, IL, USA.
¹¹ School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
¹² State Key Laboratory of Reproductive Medicine, Center for Global Health, Gusu School, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China. binshen@njmu.edu.cn.
¹³ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁴ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁵ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁶ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁷ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁸ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁹ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.

^# Contributed equally.

PMID: 35606490
DOI: 10.1038/s41556-022-00915-x

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

You Wu et al. Nat Cell Biol. 2022 Jun.

. 2022 Jun;24(6):917-927.

doi: 10.1038/s41556-022-00915-x. Epub 2022 May 23.

Authors

Affiliations

¹ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
² Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
³ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China.
⁴ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁵ State Key Laboratory of Reproductive Medicine, Center for Global Health, Gusu School, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.
⁶ Center for Reproductive Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
⁷ Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁸ State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
⁹ Center for Reproductive Medicine, Cheeloo College of Medicine, Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
¹⁰ Department of Chemistry, The University of Chicago, Chicago, IL, USA.
¹¹ School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
¹² State Key Laboratory of Reproductive Medicine, Center for Global Health, Gusu School, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China. binshen@njmu.edu.cn.
¹³ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁴ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁵ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China. gaoyawei@tongji.edu.cn.
¹⁶ Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁷ Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁸ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China. gaoshaorong@tongji.edu.cn.
¹⁹ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. gaoshaorong@tongji.edu.cn.

^# Contributed equally.

PMID: 35606490
DOI: 10.1038/s41556-022-00915-x

Abstract

N⁶-methyladenosine (m⁶A) and its regulatory components play critical roles in various developmental processes in mammals. However, the landscape and function of m⁶A in early embryos remain unclear owing to limited materials. Here we developed a method of ultralow-input m⁶A RNA immunoprecipitation followed by sequencing to reveal the transcriptome-wide m⁶A landscape in mouse oocytes and early embryos and found unique enrichment and dynamics of m⁶A 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 m⁶A methyltransferase complex, was essential for m⁶A deposition on maternal mRNAs that undergo decay after zygotic genome activation and MTA transcripts to maintain their stability in oocytes. Interestingly, m⁶A methyltransferases, especially METTL3, deposited m⁶A 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 m⁶A 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.

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

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

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