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

作者：Haiyuan Mu, Ting Zhang, Ying Yang, Ying Yang, Danru Zhang, Jie Gao, Liang Yue, Liang Yue, Dengfeng Gao, Bingbo Shi, Yue Han, Liang Zhong, Xinze Chen, Zhen‐Bo Wang, Zhen Lin, Ming‐Han Tong, Qing‐Yuan Sun, Yun-Gui Yang, Yun‐Gui Yang, Jianyong Han · 发表于：Cell Death and Disease · 年份：2021 · DOI：10.1038/s41419-021-04272-9 · 被引用次数：92 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、RNA Research and Splicing

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.