Conversely, NAT10 is guided towards its two target sites in rRNA by specialized small nucleolar RNAs 9. The deposition of ac 4C at its two tRNA targets (tRNA-Ser and tRNA-Leu) requires an additional adaptor protein-THUMPD1 in humans and Tan1 in yeast 1-and has been implicated in tRNA stability 7, 8. NAT10 and Kre33 are essential in humans and yeast, respectively, and the four target sites of these enzymes in rRNA and tRNA are also conserved between these two distant eukaryotes 1– 3. Ac 4C occurs in all domains of life, and its formation is catalysed by the acetyltransferases NAT10 in humans and Kre33 in yeast 1– 3. Perhaps the most well conserved of these mechanisms is the enzymatic modification of RNA to form the acetylated nucleobase ac 4C. Our studies quantitatively define the ac 4C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease 4– 6.Īcetylation is an ancient mechanism that regulates biomolecular function. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac 4C and its potential thermoadaptive role. Ac 4C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac 4C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. In human and yeast mRNAs, ac 4C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. Here we report ac 4C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac 4C at single-nucleotide resolution. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. N 4-acetylcytidine (ac 4C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA 1– 3.
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