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Cross-Talk between Dnmt2-Dependent tRNA Methylation and Queuosine Modification.

Ann E Ehrenhofer-Murray1

  • 1Institut für Biologie, Humboldt-Universität zu Berlin, 10099 Berlin, Germany. ann.ehrenhofer-murray@hu-berlin.de.

Biomolecules
|February 18, 2017
PubMed
Summary

Dnmt2 enzymes methylate transfer RNA (tRNA), not DNA. Their activity is nutritionally regulated by queuosine, a micronutrient essential for tRNA function and organismal health.

Keywords:
Dnmt2Pmt1anticodon modificationepitranscriptomicsqueuinequeuosinetRNA cleavagetranslation

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Epigenetics

Background:

  • Dnmt2 enzymes were initially misclassified as DNA methyltransferases.
  • Recent findings reveal Dnmt2 enzymes are actually transfer RNA (tRNA) methyltransferases, specifically methylating cytosine-5 at position 38 (m5C38) of tRNAAsp.
  • The nucleotide queuosine, a hypermodified guanine analog, is crucial for tRNA function.

Purpose of the Study:

  • To review the current knowledge of Dnmt2 methylation and queuosine modification.
  • To explore the functional relationship between Dnmt2 activity, queuosine presence, and translation.
  • To discuss the organismal consequences of lacking these modifications.

Main Methods:

  • Literature review of studies on Dnmt2 enzymes and queuosine modification.
  • Analysis of in vivo and in vitro data from Schizosaccharomyces pombe.
  • Discussion of existing models and implications.

Main Results:

  • Dnmt2 enzymes are tRNA methyltransferases, not DNA methyltransferases.
  • Dnmt2 activity in S. pombe is nutritionally regulated by the presence of queuosine in tRNAAsp.
  • Queuosine significantly stimulates Dnmt2 activity both in vivo and in vitro.
  • Eukaryotes salvage queuosine from external sources, as they cannot synthesize it.

Conclusions:

  • Dnmt2 methylation and queuosine modification are linked processes with significant roles in translation.
  • The absence of these modifications can lead to organismal consequences.
  • Understanding the interplay between Dnmt2 and queuosine provides insights into micronutrient roles and epigenetic regulation.