The RNA m6A landscape during human oocyte-to-embryo transition

Yanjiao Li; Yunhao Wang; Aylin Cengiz; Kang-Xuan Jin; Blanca Corral Castroviejo; Xiaolin Lin; Marie Indahl; Rujuan Zuo; Trine Skuland; Madeleine Fosslie; Maria Biba; Xuechen Wu; Peter Fedorcsak; Magnar Bjørås; Adam Filipczyk; John Arne Dahl; Gareth D Greggains; Kin Fai Au; Arne Klungland

doi:10.1038/s44318-025-00474-5

The RNA m⁶A landscape during human oocyte-to-embryo transition

EMBO J. 2025 Jun 4. doi: 10.1038/s44318-025-00474-5. Online ahead of print.

Authors

Yanjiao Li^#^{1

2}, Yunhao Wang^#³, Aylin Cengiz^#^{1

2}, Kang-Xuan Jin^{1

2}, Blanca Corral Castroviejo⁴, Xiaolin Lin^{1

2

5}, Marie Indahl^{2

4

6}, Rujuan Zuo¹, Trine Skuland^{2

4

6}, Madeleine Fosslie^{1

2}, Maria Biba^{2

4

6}, Xuechen Wu^{1

2}, Peter Fedorcsak^{2

4

6}, Magnar Bjørås^{1

2

5}, Adam Filipczyk¹, John Arne Dahl^{7

8}, Gareth D Greggains^{9

10

11}, Kin Fai Au¹², Arne Klungland^{13

14}

Affiliations

¹ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
² Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway.
³ Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Reproductive Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁵ Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7491, Trondheim, Norway.
⁶ Division of Gynaecology and Obstetrics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. j.a.dahl@medisin.uio.no.
⁸ Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway. j.a.dahl@medisin.uio.no.
⁹ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. g.d.greggains@ous-research.no.
¹⁰ Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway. g.d.greggains@ous-research.no.
¹¹ Department of Reproductive Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway. g.d.greggains@ous-research.no.
¹² Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. kinfai@umich.edu.
¹³ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. arne.klungland@medisin.uio.no.
¹⁴ Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway. arne.klungland@medisin.uio.no.

^# Contributed equally.

PMID: 40467862
DOI: 10.1038/s44318-025-00474-5

Abstract

RNA N⁶-methyladenosine (m⁶A, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic m⁶A profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA m⁶A landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. m⁶A-modified genes are involved in regulation of gene transcription, while unmodified genes are mainly associated with basic metabolic processes. Maternal decay mRNAs exhibit a propensity for m⁶A modifications, and these genes are targeted by miRNAs. m⁶A modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent m⁶A enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. m⁶A inhibitor leads to m⁶A erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of m⁶A during early human embryo development.

Keywords: Human Early Embryos; Retrotransposons; Zygotic Genome Activation; m6A.

Abstract

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