METTL3-mediated mRNA N(6)-methyladenosine is required for oocyte and follicle development in mice.
METTL3-mediated mRNA N(6)-methyladenosine is required for oocyte and follicle development in mice.
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METTL3 介导的 mRNA N-6-甲基腺苷是小鼠卵母细胞和卵泡发育所必需的
DOI：
10.1038/s41419-021-04272-9
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发表时间：
2021-10-23
影响因子：
9
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Mu H;Zhang T;Yang Y;Zhang D;Gao J;Li J;Yue L;Gao D;Shi B;Han Y;Zhong L;Chen X;Wang ZB;Lin Z;Tong MH;Sun QY;Yang YG;Han J
卵泡的正常发育对产生成熟的卵母细胞非常重要，而卵母细胞对维持女性生育力至关重要。这种复杂的生物学过程需要精确的基因调控。N6-甲基腺苷（m6 A）是mRNA中最丰富的修饰，参与许多RNA代谢过程，包括RNA剪接、翻译、稳定性和降解。在这里，我们报告说，m6 A在卵母细胞和卵泡发育过程中起着至关重要的作用。用Gdf 9-Cre对关键的m6 A甲基转移酶Mettl 3的卵母细胞特异性失活导致卵母细胞中DNA损伤积累、有缺陷的卵泡发育和异常排卵。从机制上讲，来自卵母细胞的组合RNA-seq和m6 A甲基化RNA免疫沉淀测序（MeRIP-seq）数据显示，我们发现胃L3靶向Itsn 2进行m6 A修饰，然后增强其稳定性以影响卵母细胞减数分裂。总之，我们的研究结果突出了mRNA m6 A修饰在卵泡发育和卵母细胞生长过程中RNA稳定性协调中的关键作用。
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.
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