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Dynamic modulation of Dnmt2-dependent tRNA methylation by the micronutrient queuine
Martin Müller1, Mark Hartmann2, Isabelle Schuster3
1Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Nucleic Acids Research
|October 2, 2015
Summary
Environmental queuine (Q) modifies tRNA, enhancing Dnmt2 enzyme activity. This study reveals how diet-derived nutrients regulate tRNA methylation, impacting gene expression.
Area of Science:
- Molecular Biology
- Epigenetics
- RNA Biology
Background:
- Dnmt2 enzymes are crucial for tRNA methylation at C38.
- Queuosine (Q) is a modified nucleobase found in tRNA.
- The role of queuine in regulating Dnmt2 activity is not well understood.
Purpose of the Study:
- To investigate the effect of queuosine modification on Dnmt2 enzyme activity.
- To explore the environmental regulation of tRNA methylation.
- To identify novel tRNA methylation sites.
Main Methods:
- Enzyme activity assays using modified and unmodified tRNA substrates.
- In vivo methylation analysis in Schizosaccharomyces pombe grown in media with and without queuine.
- Genetic analysis involving the eukaryotic tRNA-guanine transglycosylase enzyme.
- Global tRNA methylation profiling in S. pombe.
Main Results:
- Dnmt2 homologs Pmt1 (S. pombe) and DnmA (Dictyostelium discoideum) activity is significantly stimulated by queuosine-modified tRNA.
- In vivo tRNA methylation levels increased in cells grown in queuine-containing medium.
- Queuine-stimulated methylation was dependent on eukaryotic tRNA-guanine transglycosylase.
- Pmt1 exhibits specific methylation of tRNA(Asp) and a novel Pmt1- and Q-independent methylation site at C34 of tRNA(Pro) was identified.
Conclusions:
- Environmental queuine acts as a nutrient that modulates tRNA methylation by enhancing Dnmt2 activity.
- This study uncovers a link between diet, tRNA modification, and gene expression regulation.
- Dnmt2 enzyme activity and substrate specificity can be influenced by tRNA modifications.
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