At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells
Abstract
Sequences flanking the AUG initiator codon influence its recognition by eukaryotic ribosomes. From a comparison of several hundred mRNA sequences, CCA/GCCAUGG emerged as the consensus sequence for initiation in higher eukaryotes. Systematic mutagenesis of a cloned preproinsulin gene confirmed the facilitating effect of A or G in position -3 (i.e. 3 nucleotides upstream from the AUG codon), C in positions -1 and -2, and G immediately following the AUG codon. The analysis of a new set of mutants now reveals that sequences slightly farther upstream are also influential, the optimal context for initiation being (GCC)GCCA/GCCAUGG. Possible mechanistic implications of the repeating GCC motif are discussed.
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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 [40]
The Kozak consensus for mammalian genes that enhances translation initiation is GCCRCCAUGG, where AUG is the start codon.
“The Kozak consensus for mammalian genes that enhances translation initiation is GCCRCCAUGG [40,46], where AUG is the start codon.”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [40]
Efficient translation initiation in mammalian species depends mainly on the secondary structure that may embed the Kozak consensus to obscure essential translation initiation signals.
“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 [40]
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- Authors
- Kozak, M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Kozak, Marilyn
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1987-08
- Volume
- 196
- Issue
- 4
- Pages
- 947-950
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2065905166
- Cited by
- 1,182
- References
- 0
- Citations by year
- 2026: 19 · 2025: 9 · 2024: 12 · 2023: 13 · 2022: 22 · 2021: 20 · 2020: 21 · 2019: 13 · 2018: 13 · 2017: 20 · 2016: 21 · 2015: 12 · 2014: 29 · 2013: 29 · 2012: 17
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 33915)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- translation initiation, initiator codon, AUG codon, Kozak sequence, codon context, mammalian cells, mutagenesis
- MeSH terms
- Base Sequence, Codon, Insulin, Mutation, Proinsulin, Protein Precursors, RNA, Messenger, Protein Biosynthesis
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