N4-Acetylcytidine is an extraordinary bioactive compound, widely used in the research of viral afflictions. It can unyieldingly thwart viral replication and diminish the onerous viral burden.
Reference Reading
1. NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression
Ganping Wang, Ming Zhang, Yiming Zhang, Yanqi Xie, Jiepeng Zou, Jianye Zhong, Zhijia Zheng, Xianghui Zhou, Yuhang Zheng, Binshen Chen, Chunxiao Liu. Clin Transl Med. 2022 May;12(5):e738. doi: 10.1002/ctm2.738.
Dysregulation of the epitranscriptome causes abnormal expression of oncogenes in the tumorigenic process. Previous studies have shown that NAT10 can regulate mRNA translation efficiency through RNA acetylation. However, the role of NAT10-mediated acetylation modification in bladder cancer remains elusive. The clinical value of NAT10 was estimated according to NAT10 expression pattern based on TCGA data set and the tumor tissue array. Acetylated RNA immunoprecipitation sequencing was utilized to explore the role of NAT10 in mRNA ac4C modification. Translation efficiency and mRNA stability assay were applied to study the effect of NAT10-deletion on target genes. The nude mouse model and genetically engineered mice were conducted to further verify the characteristics of NAT10 in promoting BLCA progression and regulating downstream targets. NAT10 was essential for the proliferation, migration, invasion, survival and the stem-cell-like properties of bladder cancer cell lines. NAT10 was responsible for mRNA ac4C modification in BLCA cells, including BCL9L, SOX4 and AKT1. Deficient NAT10 in both xenograft and transgenic mouse models of bladder cancer reduced the tumor burden. Furthermore, acetylated RNA immunoprecipitation sequencing data and RNA immunoprecipitation qPCR results revealed that NAT10 is responsible for a set of ac4C mRNA modifications in bladder cancer cells. Inhibition of NAT10 led to a loss of ac4C peaks in these transcripts and represses the mRNA's stability and protein expression. Mechanistically, the ac4C reduction modification in specific regions of mRNAs resulting from NAT10 downregulation impaired the translation efficiency of BCL9L, SOX4 and AKT1 as well as the stability of BCL9L, SOX4. In summary, these findings provide new insights into the dynamic characteristics of mRNA's post-transcriptional modification via NAT10-dependent acetylation and predict a role for NAT10 as a therapeutic target in bladder cancer. NAT10 is highly expressed in BLCA patients and its abnormal level predicts bladder cancer progression and low overall survival rate. NAT10 is necessary and sufficient for BLCA tumourigenic properties. NAT10 is responsible for ac4C modification of target transcripts, including BCL9L, SOX4 and AKT1. NAT10 may serve as an effective and novel therapeutic target for BLCA.
2. NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells
Lu Chen, Wen-Jing Wang, Qiang Liu, Yu-Ke Wu, Yun-Wen Wu, Yu Jiang, Xiu-Quan Liao, Fei Huang, Yang Li, Li Shen, Chao Yu, Song-Ying Zhang, Li-Ying Yan, Jie Qiao, Qian-Qian Sha, Heng-Yu Fan. Nucleic Acids Res. 2022 Oct 28;50(19):10896-10913. doi: 10.1093/nar/gkac594.
Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.
3. The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review
Gehui Jin, Mingqing Xu, Mengsha Zou, Shiwei Duan. Mol Ther Nucleic Acids. 2020 Jun 5;20:13-24. doi: 10.1016/j.omtn.2020.01.037.
N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mRNA. At present, the research of ac4C involves a variety of detection methods. The formation of ac4C is closely related to N-acetyltransferase 10 (NAT10) and its helpers, such as putative tRNA acetyltransferase (TAN1) for tRNA ac4C and small nucleolar RNA (snoRNA) for rRNA ac4C. Also, ac4C is associated with the development, progression, and prognosis of a variety of human diseases. Here, we summarize the history of ac4C research and the detection technologies of ac4C. We then summarized the role and mechanism of ac4C in gene-expression regulation and demonstrated the relevance of ac4C to a variety of human diseases, especially cancer. Finally, we list the future challenges of the ac4C research and demonstrate a research strategy for the interactions among several abundant modified nucleosides on mRNA.
