6vla

Structural highlights

Function

NAT10_HUMAN RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621). Catalyzes ac4C modification of a broad range of mRNAs, enhancing mRNA stability and translation (PubMed:30449621). mRNA ac4C modification is frequently present within wobble cytidine sites and promotes translation efficiency (PubMed:30449621). Mediates the formation of ac4C at position 1842 in 18S rRNA (PubMed:25411247). May also catalyze the formation of ac4C at position 1337 in 18S rRNA (By similarity). Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis (PubMed:25411247, PubMed:25653167). Catalyzes the formation of ac4C in serine and leucine tRNAs (By similarity). Requires the tRNA-binding adapter protein THUMPD1 for full tRNA acetyltransferase activity but not for 18S rRNA acetylation (PubMed:25653167). In addition to RNA acetyltransferase activity, also able to acetylate lysine residues of proteins, such as histones, microtubules, p53/TP53 and MDM2, in vitro (PubMed:14592445, PubMed:17631499, PubMed:19303003, PubMed:26882543, PubMed:27993683, PubMed:30165671). The relevance of the protein lysine acetyltransferase activity is however unsure in vivo (PubMed:30449621). Activates telomerase activity by stimulating the transcription of TERT, and may also regulate telomerase function by affecting the balance of telomerase subunit assembly, disassembly, and localization (PubMed:14592445, PubMed:18082603). Involved in the regulation of centrosome duplication by acetylating CENATAC during mitosis, promoting SASS6 proteasome degradation (PubMed:31722219). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).[UniProtKB:P53914]^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]}

References

1. ↑ Lv J, Liu H, Wang Q, Tang Z, Hou L, Zhang B. Molecular cloning of a novel human gene encoding histone acetyltransferase-like protein involved in transcriptional activation of hTERT. Biochem Biophys Res Commun. 2003 Nov 14;311(2):506-13. PMID:14592445 doi:10.1016/j.bbrc.2003.09.235
2. ↑ Chi YH, Haller K, Peloponese JM Jr, Jeang KT. Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes. J Biol Chem. 2007 Sep 14;282(37):27447-27458. PMID:17631499 doi:10.1074/jbc.M703098200
3. ↑ Fu D, Collins K. Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation. Mol Cell. 2007 Dec 14;28(5):773-85. PMID:18082603 doi:10.1016/j.molcel.2007.09.023
4. ↑ Shen Q, Zheng X, McNutt MA, Guang L, Sun Y, Wang J, Gong Y, Hou L, Zhang B. NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules. Exp Cell Res. 2009 Jun 10;315(10):1653-67. PMID:19303003 doi:10.1016/j.yexcr.2009.03.007
5. ↑ Ito S, Horikawa S, Suzuki T, Kawauchi H, Tanaka Y, Suzuki T, Suzuki T. Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18 S ribosomal RNA (rRNA). J Biol Chem. 2014 Dec 26;289(52):35724-30. PMID:25411247 doi:10.1074/jbc.C114.602698
6. ↑ Sharma S, Langhendries JL, Watzinger P, Kotter P, Entian KD, Lafontaine DL. Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. Nucleic Acids Res. 2015 Feb 27;43(4):2242-58. doi: 10.1093/nar/gkv075. Epub 2015 , Feb 4. PMID:25653167 doi:http://dx.doi.org/10.1093/nar/gkv075
7. ↑ Liu X, Tan Y, Zhang C, Zhang Y, Zhang L, Ren P, Deng H, Luo J, Ke Y, Du X. NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. EMBO Rep. 2016 Mar;17(3):349-66. PMID:26882543 doi:10.15252/embr.201540505
8. ↑ Cai S, Liu X, Zhang C, Xing B, Du X. Autoacetylation of NAT10 is critical for its function in rRNA transcription activation. Biochem Biophys Res Commun. 2017 Jan 29;483(1):624-629. PMID:27993683 doi:10.1016/j.bbrc.2016.12.092
9. ↑ Liu X, Cai S, Zhang C, Liu Z, Luo J, Xing B, Du X. Deacetylation of NAT10 by Sirt1 promotes the transition from rRNA biogenesis to autophagy upon energy stress. Nucleic Acids Res. 2018 Oct 12;46(18):9601-9616. PMID:30165671 doi:10.1093/nar/gky777
10. ↑ Arango D, Sturgill D, Alhusaini N, Dillman AA, Sweet TJ, Hanson G, Hosogane M, Sinclair WR, Nanan KK, Mandler MD, Fox SD, Zengeya TT, Andresson T, Meier JL, Coller J, Oberdoerffer S. Acetylation of Cytidine in mRNA Promotes Translation Efficiency. Cell. 2018 Dec 13;175(7):1872-1886.e24. PMID:30449621 doi:10.1016/j.cell.2018.10.030
11. ↑ Wang T, Zou Y, Huang N, Teng J, Chen J. CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by Modulating HsSAS-6 Degradation. Cell Rep. 2019 Nov 12;29(7):2078-2091.e5. PMID:31722219 doi:10.1016/j.celrep.2019.10.028
12. ↑ Singh S, Vanden Broeck A, Miller L, Chaker-Margot M, Klinge S. Nucleolar maturation of the human small subunit processome. Science. 2021 Sep 10;373(6560):eabj5338. doi: 10.1126/science.abj5338. Epub 2021 , Sep 10. PMID:34516797 doi:http://dx.doi.org/10.1126/science.abj5338