More than two decades ago Marilyn Kozak proposed the scanning model of translation initiation, whereby translation is initiated at the first AUG codon that is in a particular context. In this article, we re-examine the context of initiator codons using a large dataset of curated human transcripts. We 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 mismatches from the consensus sequence, CCACCaugG. Also, in a large fraction of transcripts, the sequences surrounding the initiator codon deviate more from the consensus than those surrounding upstream AUGs, indicating that translation initiation from downstream AUGs is more common than generally believed.
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