TY - JOUR
T1 - Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
AU - Sas-Chen, Aldema
AU - Thomas, Justin M.
AU - Matzov, Donna
AU - Taoka, Masato
AU - Nance, Kellie D.
AU - Nir, Ronit
AU - Bryson, Keri M.
AU - Shachar, Ran
AU - Liman, Geraldy L.S.
AU - Burkhart, Brett W.
AU - Gamage, Supuni Thalalla
AU - Nobe, Yuko
AU - Briney, Chloe A.
AU - Levy, Michaella J.
AU - Fuchs, Ryan T.
AU - Robb, G. Brett
AU - Hartmann, Jesse
AU - Sharma, Sunny
AU - Lin, Qishan
AU - Florens, Laurence
AU - Washburn, Michael P.
AU - Isobe, Toshiaki
AU - Santangelo, Thomas J.
AU - Shalev-Benami, Moran
AU - Meier, Jordan L.
AU - Schwartz, Schraga
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/7/23
Y1 - 2020/7/23
N2 - N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA1–3. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac4C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac4C at single-nucleotide resolution. In human and yeast mRNAs, ac4C sites are not detected but can be induced—at a conserved sequence motif—via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac4C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac4C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac4C and its potential thermoadaptive role. Our studies quantitatively define the ac4C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease4–6.
AB - N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA1–3. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac4C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac4C at single-nucleotide resolution. In human and yeast mRNAs, ac4C sites are not detected but can be induced—at a conserved sequence motif—via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac4C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac4C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac4C and its potential thermoadaptive role. Our studies quantitatively define the ac4C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease4–6.
UR - http://www.scopus.com/inward/record.url?scp=85086505827&partnerID=8YFLogxK
U2 - 10.1038/s41586-020-2418-2
DO - 10.1038/s41586-020-2418-2
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C2 - 32555463
AN - SCOPUS:85086505827
SN - 0028-0836
VL - 583
SP - 638
EP - 643
JO - Nature
JF - Nature
IS - 7817
ER -