Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
N 4 -acetylcytidine (ac 4 C) 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 . However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac...
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Published in | Nature (London) Vol. 583; no. 7817; pp. 638 - 643 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
23.07.2020
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | N
4
-acetylcytidine (ac
4
C) 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
. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac
4
C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac
4
C at single-nucleotide resolution. In human and yeast mRNAs, ac
4
C 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 ac
4
C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac
4
C 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 ac
4
C and its potential thermoadaptive role. Our studies quantitatively define the ac
4
C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease
4
–
6
.
A method termed ac
4
C-seq is introduced for the transcriptome-wide mapping of the RNA modification
N
4
-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Israel Science Foundation USDOE Office of Science (SC) European Union (EU) SC0014597; 543165; 714023; ZIA BC011488-06; R01GM112639; R01GM100329 National Institutes of Health (NIH) Author contributions A.S.-C., J.M.T., D.M., M.S.-B., J.L.M. and S. Schwartz conceived and planned the experiments. A.S.-C. and J.M.T. developed the methodology; D.M. and M.S.-B. conducted cryo-EM and ribosome purification experiments; G.L.S.L., B.W.B. and T.J.S. performed archaeal biology and genetics; M.J.L., L.F. and M.P.W. conducted proteomics experiments; M.T., Y.N. and T.I. conducted LC–MS of partially digested ribosomes; A.S.-C. and K.D.N. performed eukaryotic overexpression analyses; A.S.-C., R.N. and S. Schwartz undertook the systematic mutagenesis screen; A.S.-C. and S. Schwartz performed the computational analysis; J.M.T., K.D.N. and S.T.G. conducted biophysical studies; K.M.B., R.S., C.A.B., S.T.G., Q.L., R.T.F., G.B.R., J.H., S. Sharma and Q.L. carried out validation experiments and follow-ups; A.S.-C., M.S.-B., J.L.M. and S. Schwartz wrote the manuscript with input from J.M.T., D.M. and T.J.S. M.S.-B., J.L.M. and S. Schwartz supervised the project and acquired funding. |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-020-2418-2 |