Abstract

Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene regulation. The most abundant modification of mRNA, N6-methyladenosine (m6A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m6A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m6A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m6A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Details

Title
METTL3-mediated mRNA N6-methyladenosine is required for oocyte and follicle development in mice
Author
Mu Haiyuan 1 ; Zhang, Ting 2 ; Yang, Ying 3 ; Zhang Danru 1 ; Gao, Jie 1 ; Li, Junhong 1 ; Liang, Yue 1 ; Gao Dengfeng 1 ; Shi Bingbo 1 ; Han, Yue 2 ; Zhong, Liang 4 ; Chen Xinze 1 ; Wang, Zhen-Bo 5   VIAFID ORCID Logo  ; Lin, Zhen 6 ; Ming-Han, Tong 6 ; Qing-Yuan, Sun 7   VIAFID ORCID Logo  ; Yun-Gui, Yang 3   VIAFID ORCID Logo  ; Han, Jianyong 1   VIAFID ORCID Logo 

1  China Agricultural University, State Key Laboratory for Agrobiotechnology, College of Biological Sciences, Beijing, China (GRID:grid.22935.3f) (ISNI:0000 0004 0530 8290) 
2  Chinese Academy of Sciences, Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); China National Center for Bioinformation, Beijing, China (GRID:grid.464209.d) (ISNI:0000 0004 0644 6935); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
3  Chinese Academy of Sciences, Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309); China National Center for Bioinformation, Beijing, China (GRID:grid.464209.d) (ISNI:0000 0004 0644 6935); University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); Chinese Academy of Sciences, Institute of Stem Cell and Regeneration, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
4  Hebei Provincial Key Laboratory of Basic Medicine for Diabetes, The Shijiazhuang Second Hospital, Shijiazhuang, Hebei, China (GRID:grid.410726.6) 
5  University of Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Beijing, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
6  University of Chinese Academy of Sciences, State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) 
7  Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China (GRID:grid.413405.7) (ISNI:0000 0004 1808 0686) 
Publication year
2021
Publication date
Nov 2021
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-021-04272-9
ProQuest document ID
2584867748
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.