Abstract
Human N-acetyltransferase 10 (NAT10) is known to be a lysine acetyltransferase that targets microtubules and histones and plays an important role in cell division. NAT10 is highly expressed in malignant tumors, and is also a promising target for therapies against laminopathies and premature aging. Here we report that NAT10 is an ATP-dependent RNA acetyltransferase responsible for formation of N(4)-acetylcytidine (ac(4)C) at position 1842 in the terminal helix of mammalian 18 S rRNA. RNAi-mediated knockdown of NAT10 resulted in growth retardation of human cells, and this was accompanied by high-level accumulation of the 30 S precursor of 18 S rRNA, suggesting that ac(4)C1842 formation catalyzed by NAT10 is involved in rRNA processing and ribosome biogenesis.
Keywords
Acetyl Coenzyme A (Acetyl-CoA)
Acetyltransferase
RNA Modification
Ribosomal RNA Processing (rRNA Processing)
Ribosome Assembly
MeSH Terms
Acetylation
Base Sequence
HEK293 Cells
HeLa Cells
Humans
Molecular Sequence Data
N-Terminal Acetyltransferase E/physiology
N-Terminal Acetyltransferases
Nucleic Acid Conformation
RNA Processing, Post-Transcriptional
RNA, Ribosomal, 18S/metabolism
Chemicals
RNA, Ribosomal, 18S
N-Terminal Acetyltransferase E
N-Terminal Acetyltransferases
NAT10 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ito Satoshi
From the Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 and.
Horikawa Sayuri
From the Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 and.
Suzuki Tateki
the Graduate School of Life Science and.
Kawauchi Hiroki
the Graduate School of Life Science and.
Tanaka Yoshikazu
the Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan.
Suzuki Takeo
From the Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 and.
Suzuki Tsutomu
From the Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 and ts@chembio.t.u-tokyo.ac.jp.
References (23)
23 references, click to expand
-
Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer.
EMBO Mol Med. 2013 Jul;5(7):983-98
PMID: 23666744
-
A single acetylation of 18 S rRNA is essential for biogenesis of the small ribosomal subunit in Saccharomyces cerevisiae.
J Biol Chem. 2014 Sep 19;289(38):26201-12
PMID: 25086048
-
Specific residues at every third position of siRNA shape its efficient RNAi activity.
Nucleic Acids Res. 2007;35(4):e27
PMID: 17259216
-
Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed in vitro.
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1033-7
PMID: 3277187
-
GSK-3β-regulated N-acetyltransferase 10 is involved in colorectal cancer invasion.
Clin Cancer Res. 2014 Sep 1;20(17):4717-29
PMID: 24982245
-
Genetics. Mysterious ribosomopathies.
Science. 2013 Aug 23;341(6148):849-50
PMID: 23970686
-
MODOMICS: a database of RNA modification pathways--2013 update.
Nucleic Acids Res. 2013 Jan;41(Database issue):D262-7
PMID: 23118484
-
Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes.
J Biol Chem. 2007 Sep 14;282(37):27447-58
PMID: 17631499
-
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. 2011 Mar 4;286(9):7139-48
PMID: 21177859
-
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
-
Mass spectrometric identification and characterization of RNA-modifying enzymes.
Methods Enzymol. 2007;425:211-29
PMID: 17673085
-
Chemical inhibition of NAT10 corrects defects of laminopathic cells.
Science. 2014 May 2;344(6183):527-32
PMID: 24786082
-
Mapping the cleavage sites on mammalian pre-rRNAs: where do we stand?
Biochimie. 2012 Jul;94(7):1521-32
PMID: 22342225
-
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
-
N4-Acetylcytidine. A previously unidentified labile component of the small subunit of eukaryotic ribosomes.
J Biol Chem. 1978 Feb 25;253(4):1101-5
PMID: 624721
-
The RNA acetyltransferase driven by ATP hydrolysis synthesizes N4-acetylcytidine of tRNA anticodon.
EMBO J. 2008 Aug 20;27(16):2194-203
PMID: 18668122
-
The structure and function of small nucleolar ribonucleoproteins.
Nucleic Acids Res. 2007;35(5):1452-64
PMID: 17284456
-
The 3D rRNA modification maps database: with interactive tools for ribosome analysis.
Nucleic Acids Res. 2008 Jan;36(Database issue):D178-83
PMID: 17947322
-
A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification.
Nat Chem Biol. 2013 Feb;9(2):105-11
PMID: 23242255
-
Human diseases of the SSU processome.
Biochim Biophys Acta. 2014 Jun;1842(6):758-64
PMID: 24240090
-
RNA helicase module in an acetyltransferase that modifies a specific tRNA anticodon.
EMBO J. 2009 May 6;28(9):1362-73
PMID: 19322199
-
Tandem mass spectrometry of small, multiply charged oligonucleotides.
J Am Soc Mass Spectrom. 1992 Jan;3(1):60-70
PMID: 24242838
-
Grand challenge commentary: RNA epigenetics?
Nat Chem Biol. 2010 Dec;6(12):863-5
PMID: 21079590