Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth

Cell. 2023 Dec 7;186(25):5517-5535.e24. doi: 10.1016/j.cell.2023.10.026. Epub 2023 Nov 21.


Transfer RNA (tRNA) modifications are critical for protein synthesis. Queuosine (Q), a 7-deaza-guanosine derivative, is present in tRNA anticodons. In vertebrate tRNAs for Tyr and Asp, Q is further glycosylated with galactose and mannose to generate galQ and manQ, respectively. However, biogenesis and physiological relevance of Q-glycosylation remain poorly understood. Here, we biochemically identified two RNA glycosylases, QTGAL and QTMAN, and successfully reconstituted Q-glycosylation of tRNAs using nucleotide diphosphate sugars. Ribosome profiling of knockout cells revealed that Q-glycosylation slowed down elongation at cognate codons, UAC and GAC (GAU), respectively. We also found that galactosylation of Q suppresses stop codon readthrough. Moreover, protein aggregates increased in cells lacking Q-glycosylation, indicating that Q-glycosylation contributes to proteostasis. Cryo-EM of human ribosome-tRNA complex revealed the molecular basis of codon recognition regulated by Q-glycosylations. Furthermore, zebrafish qtgal and qtman knockout lines displayed shortened body length, implying that Q-glycosylation is required for post-embryonic growth in vertebrates.

Keywords: RNA modification; galQ; galactosylqueuosine; manQ; mannosyl-queuosine; proteostasis; queuosine; ribosome; tRNA; translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticodon
  • Cell Line
  • Codon
  • Glycosylation
  • Humans
  • Nucleic Acid Conformation
  • Nucleoside Q / chemistry
  • Nucleoside Q / genetics
  • Nucleoside Q / metabolism
  • RNA, Transfer* / chemistry
  • RNA, Transfer* / metabolism
  • Rats
  • Swine
  • Zebrafish / metabolism


  • Anticodon
  • Codon
  • Nucleoside Q
  • RNA, Transfer