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Title:
Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping | Nature
Description:
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. A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.
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headline:Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
description: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 mRNA1â3. 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 inducedâat a conserved sequence motifâvia 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 disease4â6. A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.
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headline:Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
description: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 mRNA1â3. 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 inducedâat a conserved sequence motifâvia 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 disease4â6. A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.
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name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
type:PostalAddress
type:Organization
name:Kellie D. Nance
url:http://orcid.org/0000-0002-4396-9124
affiliation:
name:National Institutes of Health
address:
name:National Cancer Institute, National Institutes of Health, Frederick, USA
type:PostalAddress
type:Organization
name:Ronit Nir
affiliation:
name:Weizmann Institute of Science
address:
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
type:Organization
name:Keri M. Bryson
affiliation:
name:National Institutes of Health
address:
name:National Cancer Institute, National Institutes of Health, Frederick, USA
type:PostalAddress
type:Organization
name:Ran Shachar
affiliation:
name:Weizmann Institute of Science
address:
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
type:Organization
name:Geraldy L. S. Liman
affiliation:
name:Colorado State University
address:
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
type:PostalAddress
type:Organization
name:Brett W. Burkhart
affiliation:
name:Colorado State University
address:
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
type:PostalAddress
type:Organization
name:Supuni Thalalla Gamage
url:http://orcid.org/0000-0002-1045-6306
affiliation:
name:National Institutes of Health
address:
name:National Cancer Institute, National Institutes of Health, Frederick, USA
type:PostalAddress
type:Organization
name:Yuko Nobe
affiliation:
name:Tokyo Metropolitan University
address:
name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
type:PostalAddress
type:Organization
name:Chloe A. Briney
affiliation:
name:National Institutes of Health
address:
name:National Cancer Institute, National Institutes of Health, Frederick, USA
type:PostalAddress
type:Organization
name:Michaella J. Levy
affiliation:
name:Stowers Institute for Medical Research
address:
name:Stowers Institute for Medical Research, Kansas City, USA
type:PostalAddress
type:Organization
name:Ryan T. Fuchs
affiliation:
name:New England Biolabs, Inc
address:
name:RNA Research Division, New England Biolabs, Inc, Ipswich, USA
type:PostalAddress
type:Organization
name:G. Brett Robb
url:http://orcid.org/0000-0002-2382-2256
affiliation:
name:New England Biolabs, Inc
address:
name:RNA Research Division, New England Biolabs, Inc, Ipswich, USA
type:PostalAddress
type:Organization
name:Jesse Hartmann
affiliation:
name:Weizmann Institute of Science
address:
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
type:Organization
name:Sunny Sharma
url:http://orcid.org/0000-0001-8896-9016
affiliation:
name:Rutgers University
address:
name:Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, USA
type:PostalAddress
type:Organization
name:Qishan Lin
url:http://orcid.org/0000-0002-1756-1432
affiliation:
name:University at Albany
address:
name:RNA Epitranscriptomics and Proteomics Resource, University at Albany, Albany, USA
type:PostalAddress
type:Organization
name:Laurence Florens
affiliation:
name:Stowers Institute for Medical Research
address:
name:Stowers Institute for Medical Research, Kansas City, USA
type:PostalAddress
type:Organization
name:Michael P. Washburn
url:http://orcid.org/0000-0001-7568-2585
affiliation:
name:Stowers Institute for Medical Research
address:
name:Stowers Institute for Medical Research, Kansas City, USA
type:PostalAddress
type:Organization
name:Toshiaki Isobe
affiliation:
name:Tokyo Metropolitan University
address:
name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
type:PostalAddress
type:Organization
name:Thomas J. Santangelo
affiliation:
name:Colorado State University
address:
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
type:PostalAddress
type:Organization
name:Moran Shalev-Benami
affiliation:
name:Weizmann Institute of Science
address:
name:Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
type:Organization
email:[email protected]
name:Jordan L. Meier
affiliation:
name:National Institutes of Health
address:
name:National Cancer Institute, National Institutes of Health, Frederick, USA
type:PostalAddress
type:Organization
email:[email protected]
name:Schraga Schwartz
url:http://orcid.org/0000-0002-3671-9709
affiliation:
name:Weizmann Institute of Science
address:
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Stowers Institute for Medical Research, Kansas City, USA
name:RNA Research Division, New England Biolabs, Inc, Ipswich, USA
name:RNA Research Division, New England Biolabs, Inc, Ipswich, USA
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
name:Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, USA
name:RNA Epitranscriptomics and Proteomics Resource, University at Albany, Albany, USA
name:Stowers Institute for Medical Research, Kansas City, USA
name:Stowers Institute for Medical Research, Kansas City, USA
name:Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
name:Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, USA
name:Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
name:National Cancer Institute, National Institutes of Health, Frederick, USA
name:Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
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