Eukaryotic wobble uridine modifications promote a functionally redundant decoding system

Mol Cell Biol. 2008 May;28(10):3301-12. doi: 10.1128/MCB.01542-07. Epub 2008 Mar 10.


The translational decoding properties of tRNAs are modulated by naturally occurring modifications of their nucleosides. Uridines located at the wobble position (nucleoside 34 [U(34)]) in eukaryotic cytoplasmic tRNAs often harbor a 5-methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and sometimes an additional 2-thio (s(2)) or 2'-O-methyl group. Although a variety of models explaining the role of these modifications have been put forth, their in vivo functions have not been defined. In this study, we utilized recently characterized modification-deficient Saccharomyces cerevisiae cells to test the wobble rules in vivo. We show that mcm(5) and ncm(5) side chains promote decoding of G-ending codons and that concurrent mcm(5) and s(2) groups improve reading of both A- and G-ending codons. Moreover, the observation that the mcm(5)U(34)- and some ncm(5)U(34)-containing tRNAs efficiently read G-ending codons challenges the notion that eukaryotes do not use U-G wobbling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticodon / chemistry*
  • Anticodon / genetics*
  • Base Sequence
  • Codon / genetics
  • Genes, Fungal
  • Plasmids / genetics
  • Protein Biosynthesis*
  • RNA, Fungal / chemistry
  • RNA, Fungal / genetics
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Transfer RNA Aminoacylation
  • Uridine / chemistry*


  • Anticodon
  • Codon
  • RNA, Fungal
  • RNA, Transfer
  • Uridine