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Publication : METTL3-mediated mRNA N<sup>6</sup>-methyladenosine is required for oocyte and follicle development in mice.

First Author  Mu H Year  2021
Journal  Cell Death Dis Volume  12
Issue  11 Pages  989
PubMed ID  34689175 Mgi Jnum  J:313434
Mgi Id  MGI:6792112 Doi  10.1038/s41419-021-04272-9
Citation  Mu H, et al. (2021) METTL3-mediated mRNA N(6)-methyladenosine is required for oocyte and follicle development in mice. Cell Death Dis 12(11):989
abstractText  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.
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