METTL3-mediated mRNA N6-methyladenosine is required for oocyte and follicle development in mice

被引：67

作者：

Mu, Haiyuan ^{[1
]}

Zhang, Ting ^{[2
,3
,4
]}

Yang, Ying ^{[2
,3
,4
,5
]}

Zhang, Danru ^{[1
]}

Gao, Jie ^{[1
]}

Li, Junhong ^{[1
]}

Yue, Liang ^{[1
]}

Gao, Dengfeng ^{[1
]}

Shi, Bingbo ^{[1
]}

Han, Yue ^{[2
,3
,4
]}

Zhong, Liang ^{[6
]}

Chen, Xinze ^{[1
]}

Wang, Zhen-Bo ^{[4
,8
]}

Lin, Zhen ^{[7
]}

Tong, Ming-Han ^{[7
]}

Sun, Qing-Yuan ^{[9
]}

Yang, Yun-Gui ^{[2
,3
,4
,5
]}

Han, Jianyong ^{[1
]}

机构：

[1] China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing, Peoples R China

[2] Chinese Acad Sci, Coll Future Technol, Collaborat Innovat Ctr Genet & Dev, Beijing Inst Genom,Key Lab Genom & Precis Med, Beijing 100101, Peoples R China

[3] China Natl Ctr Bioinformat, Beijing 100101, Peoples R China

[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[5] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China

[6] Shijiazhuang Second Hosp, Hebei Prov Key Lab Basic Med Diabet, Shijiazhuang 050051, Hebei, Peoples R China

[7] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol,Shanghai Key La, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai 200031, Peoples R China

[8] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China

[9] Guangdong Second Prov Gen Hosp, Reprod Med Ctr, Fertil Preservat Lab, Guangzhou 510317, Peoples R China

来源：

CELL DEATH & DISEASE | 2021年 / 12卷 / 11期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

DNA METHYLATION; NUCLEAR-RNA; ACTIVATION; N6-METHYLADENOSINE; TRANSLATION; TRANSITION; MATURATION; SUBUNIT;

D O I：

10.1038/s41419-021-04272-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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, N-6-methyladenosine (m(6)A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m(6)A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m(6)A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m(6)A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m(6)A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m(6)A modification in follicle development and coordination of RNA stabilization during oocyte growth.

引用

页数：13

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