A reassessment of the translation initiation codon in vertebrates

More than two decades ago Marilyn Kozak proposed the scanning model of tran slation initiation, whereby translation is initiated at the first AUG codon that is in a particular context. In this article, we re-examine the contex t of initiator codons using a large dataset of curated human transcripts. W e find that more than 40% of transcripts contain AUG codons upstream of the actual start codon and that most authentic AUGs contain three or more mism atches from the consensus sequence, CCACCaugG. Also, in a large fraction of transcripts, the sequences surrounding the initiator codon deviate more fr om the consensus than those surrounding upstream AUGs, indicating that tran slation initiation from downstream AUGs is more common than generally belie ved.