PMID- 35937804 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220826 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation. PG - 907286 LID - 10.3389/fendo.2022.907286 [doi] LID - 907286 AB - In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. NAT10 might regulate OGA stability and expression by suppressing its degradation. To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation. CI - Copyright (c) 2022 Lin, Xiang, Huang, Zeng, Zeng, Liu, Wu, Liang, Liang, Li and Zhou. FAU - Lin, Jiayu AU - Lin J AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Xiang, Yuting AU - Xiang Y AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. AD - Department of Obstetrics and Gynecology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China. FAU - Huang, Jiana AU - Huang J AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Zeng, Haitao AU - Zeng H AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Zeng, Yanyan AU - Zeng Y AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Liu, Jiawen AU - Liu J AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Wu, Taibao AU - Wu T AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Liang, Qiqi AU - Liang Q AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Liang, Xiaoyan AU - Liang X AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Li, Jingjie AU - Li J AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Zhou, Chuanchuan AU - Zhou C AD - Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220722 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - V956696549 (Acetylglucosamine) SB - IM MH - Acetylglucosamine MH - Animals MH - Female MH - *Fertility Preservation MH - *Oocytes MH - RNA Stability PMC - PMC9352860 OTO - NOTNLM OT - N4-acetylcytidine OT - NAT10 OT - O-GlcNAc OT - OGA OT - in vitro maturation OT - oocyte OT - transcription COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/09 06:00 MHDA- 2022/08/10 06:00 PMCR- 2022/01/01 CRDT- 2022/08/08 04:08 PHST- 2022/03/29 00:00 [received] PHST- 2022/05/16 00:00 [accepted] PHST- 2022/08/08 04:08 [entrez] PHST- 2022/08/09 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.907286 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Jul 22;13:907286. doi: 10.3389/fendo.2022.907286. eCollection 2022.