The RNA m6A landscape of mouse oocytes and preimplantation embryos

Yunhao Wang; Yanjiao Li; Trine Skuland; Chengjie Zhou; Aifu Li; Adnan Hashim; Ingunn Jermstad; Shaista Khan; Knut Tomas Dalen; Gareth D Greggains; Arne Klungland; John Arne Dahl; Kin Fai Au

doi:10.1038/s41594-023-00969-x

The RNA m⁶A landscape of mouse oocytes and preimplantation embryos

Nat Struct Mol Biol. 2023 May;30(5):703-709. doi: 10.1038/s41594-023-00969-x. Epub 2023 Apr 20.

Authors

Yunhao Wang^#^{1

2}, Yanjiao Li^#^{3

4}, Trine Skuland^{5

6}, Chengjie Zhou^{7

8}, Aifu Li^{1

2}, Adnan Hashim³, Ingunn Jermstad⁹, Shaista Khan⁹, Knut Tomas Dalen⁹, Gareth D Greggains⁵, Arne Klungland^{10

11}, John Arne Dahl¹², Kin Fai Au^{13

14

15}

Affiliations

¹ Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
² Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
³ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁴ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁵ Department of Reproductive Medicine, Oslo University Hospital, Oslo, Norway.
⁶ Division of Gynaecology and Obstetrics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁷ State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
⁸ Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
⁹ Norwegian Transgenic Centre, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
¹⁰ Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. arne.klungland@ibv.uio.no.
¹¹ Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. arne.klungland@ibv.uio.no.
¹² Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway. j.a.dahl@medisin.uio.no.
¹³ Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. kinfai@med.umich.edu.
¹⁴ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. kinfai@med.umich.edu.
¹⁵ Biomedical Informatics Shared Resources, The Ohio State University, Columbus, OH, USA. kinfai@med.umich.edu.

^# Contributed equally.

Abstract

Despite the significance of N⁶-methyladenosine (m⁶A) in gene regulation, the requirement for large amounts of RNA has hindered m⁶A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m⁶A in mouse oocytes and preimplantation embryos. We define the landscape of m⁶A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m⁶A. In contrast to m⁶A-marked zygotic ally-activated genes, m⁶A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m⁶A. Our results provide a foundation for future studies exploring the regulatory roles of m⁶A in mammalian early embryonic development.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blastocyst
Embryonic Development / genetics
Gene Expression Regulation, Developmental*
Mammals / genetics
Mice
MicroRNAs* / metabolism
Oocytes / metabolism
Zygote

Substances

MicroRNAs

Abstract

Publication types

MeSH terms

Substances

Grants and funding