NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation in vitro

Xiang, Yuting; Zhou, Chuanchuan; Guo, Qi; Huang, Jiana; Wu, Taibao; Liu, Jiawen; Liang, Qiqi; Zeng, Haitao; Liang, Xiaoyan

doi:10.3389/fcell.2021.704341

Cited by 18 publications

(14 citation statements)

References 43 publications

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“…We have previously reported that NAT10 depletion resulted in retarded meiotic progression in mouse oocytes, and NAT10mediated ac4C modification was a crucial regulator during oocyte maturation (20). In the current study, we knocked down NAT10 in GV stage mouse oocytes and performed transcriptome analysis to further identify the regulated genes and investigated the underlying mechanisms.…”

Section: Expression Profiling Of Nat10-depleted Mouse Oocytesmentioning

confidence: 85%

“…The purpose of this study is to explore the important downstream genes and mechanisms of NAT10-mediated ac4C modification during oocyte maturation. In a previous study, we found that ac4C downregulation after NAT10 KD inhibited oocyte maturation, but the underlying mechanisms remained unknown (20). To further explore the underlying mechanisms, we conducted a transcriptomic study on oocytes with NAT10 KD and analyzed it with ac4C RIP data jointly (28).…”

Section: Discussionmentioning

confidence: 99%

“…Our team has previously demonstrated that NAT10-mediated ac4C modification affected oocyte maturation. In the NAT10 KD group, GV stage oocytes could not reach a satisfying first polar body extrusion rate compared with the negative control one (20). However, related downstream genes and potential mechanisms underneath it remain unclear.…”

Section: Introductionmentioning

confidence: 86%

“…In addition, the oocytes were transferred to the antibody-containing Opti-MEM medium (total volume of 5 ml), which were then transferred into the electrode groove and waited to be electroporated. The electroporation procedure was executed according to what we have reported (1-ms pulse width, 30 volts in amplitude, and 4 pulses at intervals of 50 ms) (20). For the experimental group, we electroporated Trim 21 mRNA and NAT10 antibody or OGA antibody in Opti-MEM medium at a final concentration of 200 ng/ml into GV stage oocytes.…”

Section: Nat10/oga Knockdown By Trim-away and Electroporationmentioning

confidence: 99%

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NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

et al. 2022

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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.

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Section: Expression Profiling Of Nat10-depleted Mouse Oocytesmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Nat10/oga Knockdown By Trim-away and Electroporationmentioning

confidence: 99%

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NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

et al. 2022

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“…Hutchinson-Gilford progeria syndrome (HGPS) 47 , epithelial ovarian cancer 48 , breast cancer 16 , and spermatogenesis 19 , and is most recently implicated in oocyte in vitro maturation (IVM) 49 . Mature oocytes are specialized, transcriptionally inert cells that almost exclusively contribute to the cytoplasm of zygotes when fertilized by sperm.…”

Section: Dysregulated Expression Of Nat10 Has Been Recently Linked To...mentioning

confidence: 99%

Maternal N-acetyltransferase 10 (NAT10) orchestrates oocyte meiotic cell-cycle progression and maturation in mice

Bao

Jiang

Zhu

et al. 2022

Preprint

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In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels; however, the factors underlying this sophisticated but explicit process during oocyte development remain largely unclear. Here we characterized the function of N-acetyltransferase 10 (Nat10), which was previously recognized as a "writer" for N4-acetylcytidine (ac4C) deposited on RNA molecules. We generated two germline-specific Nat10 knockout mouse models in the embryonic gonad and in postnatal growing oocytes, and another two tamoxifen-inducible Nat10 deletion models. We provided genetic evidence showing that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation in mice. Intriguingly, we discovered that Nat10 is required for sculpting the maternal transcriptome through timely degradation of polyA tail mRNAs during the Maternal-to-Zygotic transition (MZT). Importantly, we developed a novel method that outperformed the conventional methods for examining the polyA tail length (PAT), termed Hairpin Adaptor-polyA tail length (HA-PAT), in terms of the cost, sensitivity and efficiency. In summary, these findings altogether provide solid genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development, and lay a solid foundation for future mechanistic studies of varied domains of NAT10.

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N‐acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4‐acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA

Zheng

Wang

Zhou

et al. 2022

Cancer Communications

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Background: N-acetyltransferase 10 (NAT10) is the only enzyme known to mediate the N4-acetylcytidine (ac4C) modification of mRNA and is crucial for mRNA stability and translation efficiency. However, its role in cancer development and prognosis has not yet been explored. This study aimed to examine the possible role of NAT10 in colon cancer. Methods: The expression levels of NAT10 were evaluated by immunohistochemical analyses with a colon cancer tissue microarray, and its prognostic value in patients was further analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze NAT10 expression in harvested colon cancer tissues and cell lines. Stable NAT10-knockdown and NAT10-overexpressing colon cancer cell lines were constructed using lentivirus.The biological functions of NAT10 in colon cancer cell lines were analyzed in

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NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation in vitro

Cited by 18 publications

References 43 publications

NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

Maternal N-acetyltransferase 10 (NAT10) orchestrates oocyte meiotic cell-cycle progression and maturation in mice

N‐acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4‐acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA

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