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Dynamic reprogramming and function of RNA N6-methyladenosine modification during porcine early embryonic development

Published online by Cambridge University Press:  23 April 2021

Tong Yu ,
Xin Qi ,
Ling Zhang ,
Wei Ning ,
Di Gao ,
Tengteng Xu ,
Yangyang Ma ,
Jason G Knott ,
Anucha Sathanawongs  and
Zubing Cao Open the ORCID record for Zubing Cao [Opens in a new window]
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Tong Yu
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Xin Qi
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Ling Zhang
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Wei Ning
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Di Gao
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Tengteng Xu
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Yangyang Ma
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Jason G Knott
Affiliation:
Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI48824, USA
Anucha Sathanawongs
Affiliation:
Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, A. Muang 50100, Thailand
Zubing Cao*
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
Yunhai Zhang*
Affiliation:
Anhui Province Key Laboratory of Local Livestock and Poultry, Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
*
Authors for correspondence: Yunhai Zhang and Zubing Cao. College of Animal Science and Technology, Anhui Agricultural University, Hefei230036, China. E-mail: yunhaizhang@ahau.edu.cn; zubingcao@ahau.edu.cn
Authors for correspondence: Yunhai Zhang and Zubing Cao. College of Animal Science and Technology, Anhui Agricultural University, Hefei230036, China. E-mail: yunhaizhang@ahau.edu.cn; zubingcao@ahau.edu.cn
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Summary

N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.

Keywords

Early embryosm6ANuclear transferPigReprogramming
Type
Research Article
Information
Zygote , Volume 29 , Issue 6 , December 2021 , pp. 417 - 426
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this study.

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