Queuine links translational control in eukaryotes to a micronutrient from bacteria

Nucleic Acids Res. 2019 Apr 23;47(7):3711-3727. doi: 10.1093/nar/gkz063.


In eukaryotes, the wobble position of tRNA with a GUN anticodon is modified to the 7-deaza-guanosine derivative queuosine (Q34), but the original source of Q is bacterial, since Q is synthesized by eubacteria and salvaged by eukaryotes for incorporation into tRNA. Q34 modification stimulates Dnmt2/Pmt1-dependent C38 methylation (m5C38) in the tRNAAsp anticodon loop in Schizosaccharomyces pombe. Here, we show by ribosome profiling in S. pombe that Q modification enhances the translational speed of the C-ending codons for aspartate (GAC) and histidine (CAC) and reduces that of U-ending codons for asparagine (AAU) and tyrosine (UAU), thus equilibrating the genome-wide translation of synonymous Q codons. Furthermore, Q prevents translation errors by suppressing second-position misreading of the glycine codon GGC, but not of wobble misreading. The absence of Q causes reduced translation of mRNAs involved in mitochondrial functions, and accordingly, lack of Q modification causes a mitochondrial defect in S. pombe. We also show that Q-dependent stimulation of Dnmt2 is conserved in mice. Our findings reveal a direct mechanism for the regulation of translational speed and fidelity in eukaryotes by a nutrient originating from bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticodon / genetics
  • Asparagine / genetics
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA, Mitochondrial / genetics
  • Eukaryota / genetics
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Methylation
  • Mice
  • Micronutrients / genetics*
  • Protein Biosynthesis / genetics*
  • RNA, Transfer / genetics
  • Ribosomes / genetics
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / genetics*
  • Tyrosine / genetics


  • Anticodon
  • DNA, Mitochondrial
  • Micronutrients
  • Schizosaccharomyces pombe Proteins
  • Tyrosine
  • Guanine
  • Asparagine
  • queuine
  • RNA, Transfer
  • Dnmt2 protein, mouse
  • DNA (Cytosine-5-)-Methyltransferases
  • Pmt1 protein, S pombe
  • 7-deazaguanine