title: Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2).
abstract: 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.
authors.affiliation: Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma 8916-5, Nara 630-0101, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Maruyama
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Tokuzawa
authors.forename: Mirei
authors.initials: M
authors.lastname: Murakami
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Oda
authors.forename: Nami
authors.initials: N
authors.lastname: Yoshikane
authors.forename: Kazuhiro W
authors.initials: KW
authors.lastname: Makabe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichisaka
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D029721:Drosophila Proteins / Q000235:genetics*; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D014176:Protein Biosynthesis; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D020798:Two-Hybrid System Techniques
chemical_list: D029721:Drosophila Proteins; C491300:EIF4G2 protein, human; D039603:Eukaryotic Initiation Factor-4G; C580572:NAT1 translation factor, Drosophila