THE ROLE OF THE TRANSLATIONAL REGULATOR NAT1 IN DEVELOPMENT

只有少数情况下，独家翻译起始非AUG密码子已被报道。我们最近证明，由E1 F4 G2编码的哺乳动物NAT 1 mRNA使用GUG作为其唯一的翻译起始密码子。在这项研究中，我们确定了从鸡，非洲爪蟾和斑马鱼的NAT 1直系同源物，并发现在所有物种中，GUG密码子也作为起始密码子。在所有物种中，GUG密码子满足非AUG起始的报告要求：最佳Kozak基序和下游发夹结构。定点突变表明，在位置-3和+4的核苷酸是关键的GUG介导的翻译起始在体外。我们发现果蝇和罗氏盐辛西娅的NAT 1同源基因也使用非AUG起始密码子，这表明非经典翻译起始的进化保守性。

Only a few cases of exclusive translation initiation at non-AUG codons have been reported. We recently demonstrated that mammalian NAT1 mRNA, encoded by E1F4G2, 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 codons also serve as the initiation codon. In all species, the GUG codons 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 roreizi also use non-AUG start codons, demonstrating evolutional conservation of the non-canonical translation initiation.