Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes
Open accessAbstract
Sequences flanking the initiator codon in eukaryotic mRNAs are not random. Out of 153 messages examined, 151 have either a purine in position -3, or a G in position +4, or both. Thus, [A/G]XXAUGG emerges as the favored sequence for eukaryotic initiation sites. Nucleotides flanking nonfunctional AUG triplets, which occur in the 5'-noncoding region of a few eukaryotic messages, are different from those found at most functional sites. Whereas most authentic initiator codons are preceded by a purine (usually A) in position -3, most nonfunctional AUGs have a pyrimidine in that position. The observed asymmetry suggests that purines in positions -3 and +4 might facilitate recognition of the AUG condon during formation of initiation complexes. To test this idea, in vitro binding studies were carried out with 32P-labeled oligonucleotides. Binding of AUG-containing oligonucleotides to wheat germ ribosomes was significantly enhanced by placing a purine in position -3 or +4. The scanning model, which postulates that 40S ribosomal subunits attach at the 5'-end of a message and migrate down to the AUG codon, is discussed in light of these new observations. A modified version of the scanning mechanism is proposed.
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Efficient translation initiation in mammalian species depends mainly on the Kozak consensus.
“Efficient translation initiation in mammalian species depends mainly on two factors [40,41]: (1) the Kozak consensus [42,43,44], and (2) the secondary structure that may embed the Kozak consensus to obscure these essential translation initiation signals [9,41,45].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [43]
In the section on nucleotides flanking the initiator codon (page unavailable), Kozak proposes that favorable flanking nucleotides improve the efficiency with which ribosomes recognize an AUG. The paper examines eukaryotic messages and tests binding to wheat-germ ribosomes; it does not establish that mammalian translation initiation depends mainly on the consensus. It also says AUG position appears to be the primary determinant of a functional initiation site. (LLM, conf=0.84)
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- Authors
- Kozak, M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Kozak, Marilyn
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1981
- Volume
- 9
- Issue
- 20
- Pages
- 5233-5252
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC327517
- OpenAlex
- W2020828649
- Cited by
- 1,242
- References
- 0
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 12 · 2020: 10 · 2019: 9 · 2018: 13 · 2017: 6 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 37.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- initiator codon, AUG codon, eukaryotic translation initiation, 5' untranslated region, ribosome binding, scanning model, 40S ribosomal subunit, oligonucleotide binding
- MeSH terms
- Base Sequence, Codon, Genetic Code, Oligoribonucleotides, Plants, Ribosomes, RNA, Messenger, Protein Biosynthesis, Triticum
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