NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation

Zheng, Jiaojiao; Tan, Ying; Liu, Xiaofeng; Zhang, Chunfeng; Su, Kunqi; Jiang, Yang; Luo, Jianyuan; Li, Li; Du, Xiaojuan

doi:10.1038/s41418-021-00899-5

Cited by 25 publications

(18 citation statements)

References 59 publications

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“…RNA decay assays indicated that relatively fewer NR2F1 transcripts remain in RE‐treated cells compared with DMSO‐treated cells and its half‐life was reduced from 693.15 to 99.02 min (Figure 4A). Previous studies have shown that NAT10 not only possesses RNA acetyltransferase activity, but also regulates the expression of histones 27–29 . To verify whether NAT10 can also regulate the stability of NR2F1 protein, we used the protein synthesis inhibitor CHX for protein stability testing, and the results showed that NR2F1 protein showed no significant changes in both the control and the NAT10 specific inhibitor group (Figure 4B,C).…”

Section: Resultsmentioning

confidence: 91%

“…ac 4 C modification has been found in numerous species and it regulates varied biological processes, such as oocyte maturation, 32 spermatogenesis, 14 cancer cell progression 11 and osteogenic differentiation. 33 Moreover, ac 4 C modification is also linked to human diseases, such as ischemic heart disease, 18 bladder cancer 10 and gastric cancer, 34 acetylating Eg5 at K771 28 and increases the transcription of human telomerase reverse transcriptase to enhance telomerase activity. 27 In 2018, Arango et al found that NAT10 was also involved in increasing mRNA ac 4 C modification in mammals.…”

Section: Nr2f1 Promotes Ectodermal Differentiation Of Hescs By Accele...mentioning

confidence: 99%

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NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Ge,

Wang,

2023

Cell Proliferation

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Cell fate determination in mammalian development is complex and precisely controlled and accumulating evidence indicates that epigenetic mechanisms are crucially involved. N4‐acetylcytidine (ac4C) is a recently identified modification of messenger RNA (mRNA); however, its functions are still elusive in mammalian. Here, we show that N‐acetyltransferase 10 (NAT10)‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells (hESCs) by acetylating nuclear receptor subfamily 2 group F member 1 (NR2F1) mRNA to enhance translation efficiency (TE). Acetylated RNA immunoprecipitation sequencing (acRIP‐seq) revealed that levels of ac4C modification were higher in ectodermal neuroepithelial progenitor (NEP) cells than in hESCs or mesoendoderm cells. In addition, integrated analysis of acRIP‐seq and ribosome profiling sequencing revealed that NAT10 catalysed ac4C modification to improve TE in NEP cells. RIP‐qRT‐PCR analysis identified an interaction between NAT10 and NR2F1 mRNA in NEP cells and NR2F1 accelerated the nucleus‐to‐cytoplasm translocation of yes‐associated protein 1, which contributed to ectodermal differentiation of hESCs. Collectively, these findings point out the novel regulatory role of ac4C modification in the early ectodermal differentiation of hESCs and will provide a new strategy for the treatment of neuroectodermal defects diseases.

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Section: Resultsmentioning

confidence: 91%

Section: Nr2f1 Promotes Ectodermal Differentiation Of Hescs By Accele...mentioning

confidence: 99%

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Ge,

Wang,

2023

Cell Proliferation

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“…Human cancer cell lines are typical in vitro model systems commonly applied in drug discovery and basic research 41–44 . More than 100 cell lines have been established as CRC cell lines from cell line banks worldwide.…”

Section: Typical Crc Preclinical Modelsmentioning

confidence: 99%

“…Human cancer cell lines are typical in vitro model systems commonly applied in drug discovery and basic research. 41 , 42 , 43 , 44 More than 100 cell lines have been established as CRC cell lines from cell line banks worldwide. Cell line–derived xenograft (CDX) models developed by implanting cancer cell lines into immunodeficient mice contribute to the discovery of underlying mechanisms and the development of cancer drugs.…”

Section: Typical Crc Preclinical Modelsmentioning

confidence: 99%

Patient‐derived xenograft model in colorectal cancer basic and translational research

Liu

Xin

Wang

2022

Anim Models and Exp Med

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Colorectal cancer (CRC), one of the most deadly cancers, is the fourth most common cause of cancer-related deaths. 1 Currently, surgery is the main treatment option for primary and metastatic CRC, and chemotherapy and targeted drugs are regularly used as adjuvant regimens. [2][3][4] Despite improvements in screening and treatment, the number of individuals newly diagnosed is increasing rapidly. Moreover, metastasis, recurrence, and chemoresistance are common in CRC patients after treatment, which leads to the dismal prognosis and high mortality of CRC patients. [5][6][7] These issues lead to the need for more advancements in CRC treatment. About 5% of CRCs are hereditary tumor syndromes, such as familial adenomatous polyposis (FAP) and Lynch syndrome. 8 Most of the CRCs are sporadic as the comprehensive effects of various factors, including somatic genetic alterations, chronic inflammation, lifestyle, and environmental stimuli. 9 These genetic and nongenetic risk factors work together to promote CRC development and progression. [10][11][12][13] To date, the mechanisms involved in the interactions of these factors driving CRC development and progression are

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“…Second, as described above, oocyte development is under tight, spatiotemporally specific regulation through discontinuous meiotic cell-cycle progression -rapid progression at early meiotic prophase I in the embryonic gonad, lengthened late prophase I arrest at diplotene during prepubertal development, and quick cytoplasmic and nuclear maturation during the GV-MII transition. Compelling studies have shown evidence related to Nat10's function in cell-cycle control in somatic cells 16,17,18 . Interestingly, specific deletion of Nat10 in the male germline elicited severe defects resulting in male infertility owing to corrupted meiotic cell-cycle progression in mice 19 .…”

Section: Introductionmentioning

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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NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation

Cited by 25 publications

References 59 publications

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Patient‐derived xenograft model in colorectal cancer basic and translational research

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

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NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation

Cited by 25 publications

References 59 publications

NAT10‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

Patient‐derived xenograft model in colorectal cancer basic and translational research

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

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NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

NAT10‐mediated ac⁴C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA