Advances of NAT10 in Diseases: Insights from Dual Properties As Protein and RNA Acetyltransferase

Overview

Journal Cell Biol Toxicol

Publisher Springer

Specialties Cell Biology
Toxicology

Date 2024 Dec 26

PMID 39725720

Authors

Bin Xiao

Shunhong Wu

Yan Tian

Weikai Huang

Guangzhan Chen

Dongxin Luo

Yishen Cai

Ming Chen

Yuqian Zhang

Chuyan Liu

Junxiu Zhao

Linhai Li

Affiliations

Soon will be listed here.

Abstract

N-acetyltransferase 10 (NAT10) is a member of the Gcn5-related N-acetyltransferase (GNAT) family and it plays a crucial role in various cellular processes, such as regulation of cell mitosis, post-DNA damage response, autophagy and apoptosis regulation, ribosome biogenesis, RNA modification, and other related pathways through its intrinsic protein acetyltransferase and RNA acetyltransferase activities. Moreover, NAT10 is closely associated with the pathogenesis of tumors, Hutchinson-Gilford progeria syndrome (HGPS), systemic lupus erythematosus, pulmonary fibrosis, depression and host-pathogen interactions. In recent years, mRNA acetylation has emerged as a prominent focus of research due to its pivotal role in regulating RNA stability and translation. NAT10 stands out as the sole identified modification enzyme responsible for RNA acetylation. There remains some ambiguity regarding the similarities and differences in NAT10's actions on protein and RNA substrates. While NAT10 involves acetylation modification in both cases, which is a crucial molecular mechanism in epigenetic regulation, there are significant disparities in the catalytic mechanisms, regulatory pathways, and biological processes involved. Therefore, this review aims to offer a comprehensive overview of NAT10 as a protein and RNA acetyltransferase, covering its basic catalytic features, biological functions, and roles in related diseases.

References

Castedo M, Perfettini J, Roumier T, Andreau K, Medema R, Kroemer G . Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004; 23(16):2825-37. DOI: 10.1038/sj.onc.1207528. View

Liu Y, Wang X, Liu Y, Yang J, Mao W, Feng C . N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway. Cell Death Dis. 2023; 14(11):712. PMC: 10620198. DOI: 10.1038/s41419-023-06245-6. View

Sharma S, Langhendries J, Watzinger P, Kotter P, Entian K, Lafontaine D . Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. Nucleic Acids Res. 2015; 43(4):2242-58. PMC: 4344512. DOI: 10.1093/nar/gkv075. View

Zheng J, Tan Y, Liu X, Zhang C, Su K, Jiang Y . NAT10 regulates mitotic cell fate by acetylating Eg5 to control bipolar spindle assembly and chromosome segregation. Cell Death Differ. 2022; 29(4):846-860. PMC: 8989979. DOI: 10.1038/s41418-021-00899-5. View

Liu X, Cai S, Zhang C, Liu Z, Luo J, Xing B . Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress. Nucleic Acids Res. 2018; 46(18):9601-9616. PMC: 6182161. DOI: 10.1093/nar/gky777. View

Balmus G, Larrieu D, Barros A, Collins C, Abrudan M, Demir M . Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat Commun. 2018; 9(1):1700. PMC: 5923383. DOI: 10.1038/s41467-018-03770-3. View

Tsai K, Vasudevan A, Martinez Campos C, Emery A, Swanstrom R, Cullen B . Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability. Cell Host Microbe. 2020; 28(2):306-312.e6. PMC: 7429276. DOI: 10.1016/j.chom.2020.05.011. View

Zachau H, Dutting D, Feldmann H . The structures of two serine transfer ribonucleic acids. Hoppe Seylers Z Physiol Chem. 1966; 347(4):212-35. DOI: 10.1515/bchm2.1966.347.1.212. View

Ikeuchi Y, Kitahara K, Suzuki T . The RNA acetyltransferase driven by ATP hydrolysis synthesizes N4-acetylcytidine of tRNA anticodon. EMBO J. 2008; 27(16):2194-203. PMC: 2500205. DOI: 10.1038/emboj.2008.154. View

10.

Dunin-Horkawicz S, Czerwoniec A, Gajda M, Feder M, Grosjean H, Bujnicki J . MODOMICS: a database of RNA modification pathways. Nucleic Acids Res. 2005; 34(Database issue):D145-9. PMC: 1347447. DOI: 10.1093/nar/gkj084. View

11.

Yu X, Li S, Yao Z, Xu J, Zheng C, Liu Z . N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing. Oncogene. 2023; 42(14):1101-1116. DOI: 10.1038/s41388-023-02628-3. View

12.

Wang G, Zhang M, Zhang Y, Xie Y, Zou J, Zhong J . NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression. Clin Transl Med. 2022; 12(5):e738. PMC: 9076013. DOI: 10.1002/ctm2.738. View

13.

Drygin D, Lin A, Bliesath J, Ho C, OBrien S, Proffitt C . Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2010; 71(4):1418-30. DOI: 10.1158/0008-5472.CAN-10-1728. View

14.

Sas-Chen A, Thomas J, Matzov D, Taoka M, Nance K, Nir R . Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping. Nature. 2020; 583(7817):638-643. PMC: 8130014. DOI: 10.1038/s41586-020-2418-2. View

15.

Li D, Yuan D, Shen H, Mao X, Yuan S, Liu Q . Gremlin-1: An endogenous BMP antagonist induces epithelial-mesenchymal transition and interferes with redifferentiation in fetal RPE cells with repeated wounds. Mol Vis. 2019; 25:625-635. PMC: 6817737. View

16.

Kong R, Zhang L, Hu L, Peng Q, Han W, Du X . hALP, a novel transcriptional U three protein (t-UTP), activates RNA polymerase I transcription by binding and acetylating the upstream binding factor (UBF). J Biol Chem. 2010; 286(9):7139-48. PMC: 3044971. DOI: 10.1074/jbc.M110.173393. View

17.

Yang Q, Lei X, He J, Peng Y, Zhang Y, Ling R . N4-Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF-1α Positive Feedback Loop. Adv Sci (Weinh). 2023; 10(23):e2300898. PMC: 10427357. DOI: 10.1002/advs.202300898. View

18.

Zheng X, Wang Q, Zhou Y, Zhang D, Geng Y, Hu W . N-acetyltransferase 10 promotes colon cancer progression by inhibiting ferroptosis through N4-acetylation and stabilization of ferroptosis suppressor protein 1 (FSP1) mRNA. Cancer Commun (Lond). 2022; 42(12):1347-1366. PMC: 9759759. DOI: 10.1002/cac2.12363. View

19.

Zhang L, Li D . MORC2 regulates DNA damage response through a PARP1-dependent pathway. Nucleic Acids Res. 2019; 47(16):8502-8520. PMC: 6895267. DOI: 10.1093/nar/gkz545. View

20.

Passananti C, Floridi A, Fanciulli M . Che-1/AATF, a multivalent adaptor connecting transcriptional regulation, checkpoint control, and apoptosis. Biochem Cell Biol. 2007; 85(4):477-83. DOI: 10.1139/O07-062. View