N6-methyladenosine methyltransferase METTL3 modulates the cell cycle of granulosa cells via CCND1 and AURKB in Haimen goats.

N6-methyladenosine (m6A) plays a crucial role in many bioprocesses across species, but its function in granulosa cells during oocyte maturation is not well understood in animals, especially domestic animals. We observed an increase in m6A methyltransferase-like 3 (METTL3) in granulosa cells during oocyte maturation in Haimen goats. Our results showed that knockdown of METTL3 disrupted the cell cycle in goat granulosa cells, leading to aggravated cell apoptosis and inhibition of cell proliferation and hormone secretion. Mechanistically, METTL3 may regulate the cell cycle in goat granulosa cells by mediating Aurora kinase B (AURKB) mRNA degradation in an m6A-YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) manner and participating in AURKB transcription via the Cyclin D1 (CCND1)-Retinoblastoma protein (RB)-E2F transcription factor 1 (E2F1) pathway. Overall, our study highlights the essential role of METTL3 in granulosa cells during oocyte maturation in Haimen goats. These findings provide a theoretical basis and technical means for understanding how RNA methylation participates in oocyte maturation through granulosa cells. © 2023 Federation of American Societies for Experimental Biology.

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Zifei Liu, Lei Zhou, Dongxu Li, Honghui Lu, Liang Liu, Weijia Mao, Xiaoqing Yu, Yixuan Fan, Qunhao Huang, Feng Wang, Yongjie Wan. N6-methyladenosine methyltransferase METTL3 modulates the cell cycle of granulosa cells via CCND1 and AURKB in Haimen goats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023 Nov;37(11):e23273

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PMID: 37874265

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