RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Francesca Tuorto
  • Reinhard Liebers
  • Tanja Musch
  • Matthias Schaefer
  • Sarah Hofmann
  • Stefanie Kellner
  • Michaela Frye
  • Mark Helm
  • Georg Stoecklin
  • Frank Lyko
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000308630900010&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1038/nsmb.2357
Externe Identifier
  • Clarivate Analytics Document Solution ID: 003SF
  • PubMed Identifier: 22885326
ISSN
1545-9993
Ausgabe der Veröffentlichung
9
Zeitschrift
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Paginierung
900 - 905
Datum der Veröffentlichung
2012
Status
Published
Titel
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis
Sub types
  • Article
Ausgabe der Zeitschrift
19

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Francesca Tuorto
  • Reinhard Liebers
  • Tanja Musch
  • Matthias Schaefer
  • Sarah Hofmann
  • Stefanie Kellner
  • Michaela Frye
  • Mark Helm
  • Georg Stoecklin
  • Frank Lyko
DOI
10.1038/nsmb.2357
eISSN
1545-9985
ISSN
1545-9993
Ausgabe der Veröffentlichung
9
Zeitschrift
Nature Structural & Molecular Biology
Sprache
en
Online publication date
2012
Paginierung
900 - 905
Datum der Veröffentlichung
2012
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1038/nsmb.2357
Datum der Datenerfassung
2023
Titel
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis
Ausgabe der Zeitschrift
19

Datenquelle: Crossref

Abstract
The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylated tRNAs were substantially reduced, and loss of Dnmt2 and NSun2 was further associated with reduced rates of overall protein synthesis. These results establish a biologically important function for cytosine-C5 tRNA methylation in mammals and suggest that this modification promotes mouse development by supporting protein synthesis.
Addresses
  • Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Autoren
  • Francesca Tuorto
  • Reinhard Liebers
  • Tanja Musch
  • Matthias Schaefer
  • Sarah Hofmann
  • Stefanie Kellner
  • Michaela Frye
  • Mark Helm
  • Georg Stoecklin
  • Frank Lyko
DOI
10.1038/nsmb.2357
eISSN
1545-9985
Externe Identifier
  • PubMed Identifier: 22885326
Funding acknowledgements
  • Medical Research Council: G0800784B
  • Wellcome Trust: 079249
  • Medical Research Council: G0800784
  • Medical Research Council: G0801904
Open access
false
ISSN
1545-9993
Ausgabe der Veröffentlichung
9
Zeitschrift
Nature structural & molecular biology
Schlüsselwörter
  • Cells, Cultured
  • Animals
  • Mice, Knockout
  • Mice
  • Cytosine
  • Methyltransferases
  • RNA, Transfer
  • Cell Differentiation
  • Protein Biosynthesis
  • Gene Deletion
  • RNA Stability
  • Methylation
  • Female
  • Male
  • DNA (Cytosine-5-)-Methyltransferases
Sprache
eng
Medium
Print-Electronic
Online publication date
2012
Paginierung
900 - 905
Datum der Veröffentlichung
2012
Status
Published
Datum der Datenerfassung
2012
Titel
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
19

Datenquelle: Europe PubMed Central

Abstract
The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylated tRNAs were substantially reduced, and loss of Dnmt2 and NSun2 was further associated with reduced rates of overall protein synthesis. These results establish a biologically important function for cytosine-C5 tRNA methylation in mammals and suggest that this modification promotes mouse development by supporting protein synthesis.
Date of acceptance
2012
Autoren
  • Francesca Tuorto
  • Reinhard Liebers
  • Tanja Musch
  • Matthias Schaefer
  • Sarah Hofmann
  • Stefanie Kellner
  • Michaela Frye
  • Mark Helm
  • Georg Stoecklin
  • Frank Lyko
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/22885326
DOI
10.1038/nsmb.2357
eISSN
1545-9985
Funding acknowledgements
  • Wellcome Trust: 079249
  • Medical Research Council: G0800784
  • Medical Research Council: G0801904
Ausgabe der Veröffentlichung
9
Zeitschrift
Nat Struct Mol Biol
Schlüsselwörter
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cytosine
  • DNA (Cytosine-5-)-Methyltransferases
  • Female
  • Gene Deletion
  • Male
  • Methylation
  • Methyltransferases
  • Mice
  • Mice, Knockout
  • Protein Biosynthesis
  • RNA Stability
  • RNA, Transfer
Sprache
eng
Country
United States
Paginierung
900 - 905
PII
nsmb.2357
Datum der Veröffentlichung
2012
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2012
Titel
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
19

Datenquelle: PubMed

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