Inhibition of METTL5 improves preimplantation development of mouse somatic cell nuclear transfer embryos

in Reproduction
Authors:
Luchun Zhang Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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https://orcid.org/0000-0002-5497-8173
,
Meng Yuan Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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Xingwei Huang Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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Qianzi Cao Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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Shaogang Huang Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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https://orcid.org/0000-0002-1654-2459
,
Ruizhen Sun Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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, and
Lei Lei Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, China

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https://orcid.org/0000-0002-5239-7009

Correspondence should be addressed to L Lei; Email: lei086@ems.hrbmu.edu.cn

*(L Zhang and M Yuan contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-22-0169
Volume/Issue:
Volume 164: Issue 5
Page Range:
221–230
Article Type:
Research Article
Online Publication Date:
10 Oct 2022
Copyright:
© Society for Reproduction and Fertility 2022
Restricted access
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In brief

Several factors affect the reprogramming efficiency of nuclear transfer embryos. This study shows that inhibiting 18S rRNA m6A methyltransferase METTL5 during nuclear transfer can improve the developmental rate of nuclear transfer embryos.

Abstract

N6-methyladenosine (m6A) is one of the most important epigenetic modifications in eukaryotic RNAs, which regulates development and diseases. It is identified by several proteins. Methyltransferase-like 5 (METTL5), an enzyme that methylates 18S rRNA m6A, controls the translation of proteins and regulates pluripotency in embryonic stem cells. However, the functions of METTL5 in embryonic development have not been explored. Here, we found that Mettl5 was upregulated in somatic cell nuclear transfer (SCNT) embryos compared with normal fertilized embryos. Therefore, we hypothesized that METTL5 knockdown during the early stage of SCNT would improve the developmental rate of SCNT embryos. Notably, injection of Mettl5 siRNA (si-Mettl5) into enucleated oocytes during nuclear transfer increased the rate of development and the number of cells in blastocysts. Moreover, inhibition of METTL5 reduced the activity of phosphorylated ribosomal protein S6, decreased the levels of the repressive histone modification H3K27me3 and increased the expression of activating histone modifications H3K27ac and H3K4me3 and mRNA levels of some 2-cell-specific genes. These results expand our understanding of the role of METTL5 in early embryonic development and provide a novel idea for improving the efficiency of nuclear transfer cloning.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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