2. Academic Validation
  3. The RNA m6A landscape during human oocyte-to-embryo transition

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

  • EMBO J. 2025 Jul;44(14):4150-4180. doi: 10.1038/s44318-025-00474-5.
Yanjiao Li # 1 2,  Yunhao Wang # 3,  Aylin Cengiz # 1 2,  Kang-Xuan Jin 1 2,  Blanca Corral Castroviejo 4,  Xiaolin Lin 1 2 5,  Marie Indahl 2 4 6,  Rujuan Zuo 1,  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 Filipczyk 1,  John Arne Dahl 7 8,  Gareth D Greggains 9 10 11,  Kin Fai Au 12,  Arne Klungland 13 14
Affiliations

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.

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