Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2)

Genomics. 2005 Mar;85(3):360-71. doi: 10.1016/j.ygeno.2004.11.012.


Only a few cases of exclusive translation initiation at non-AUG codons have been reported. We recently demonstrated that mammalian NAT1 mRNA, encoded by EIF4G2, uses GUG as its only translation initiation codon. In this study, we identified NAT1 orthologs from chicken, Xenopus, and zebrafish and found that in all species, the GUG codon also serves as the initiation codon. In all species, the GUG codon fulfilled the reported requirements for non-AUG initiation: an optimal Kozak motif and a downstream hairpin structure. Site-directed mutagenesis showed that nucleotides at positions -3 and +4 are critical for the GUG-mediated translation initiation in vitro. We found that NAT1 orthologs in Drosophila melanogaster and Halocynthia roretzi also use non-AUG start codons, demonstrating evolutionary conservation of the noncanonical translation initiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Western
  • Drosophila Proteins / genetics*
  • Eukaryotic Initiation Factor-4G / chemistry
  • Eukaryotic Initiation Factor-4G / genetics*
  • Evolution, Molecular*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Biosynthesis*
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Two-Hybrid System Techniques


  • Drosophila Proteins
  • EIF4G2 protein, human
  • Eukaryotic Initiation Factor-4G
  • NAT1 translation factor, Drosophila

Associated data

  • GENBANK/AB096098
  • GENBANK/AB096099
  • GENBANK/AB096100
  • GENBANK/AB096101
  • GENBANK/AB096102
  • GENBANK/AB096103