Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes
Open accessAbstract
Recognition of an AUG initiator codon in a suboptimal context improves when a modest amount of secondary structure is introduced near the beginning of the protein-coding sequence. This facilitating effect depends on the position of the downstream stem-loop (hairpin) structure. The strongest facilitation is seen when the hairpin is separated from the preceding AUG codon by 14 nucleotides. Because 14 nucleotides corresponds to the approximate distance between the leading edge of the ribosome and its AUG-recognition center as measured by ribonuclease protection experiments, a likely explanation for the enhancing effect of a downstream hairpin is that secondary structure slows scanning, thereby providing more time for recognition of the AUG codon, and the facilitation is greatest when the 40S ribosome stalls with its AUG-recognition center directly over the AUG. The variable ability of mammalian ribosomes to initiate at non-AUG codons in vitro is also explicable by the presence or absence of a stem-loop structure just downstream from the alternative initiator codon. This may be relevant to recent reports of adventitious upstream initiation events at non-AUG codons in some vertebrate mRNAs that have structure-prone, G + C-rich leader sequences.
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Secondary structure downstream of the start codon tends to enhance recognition of start codons by eukaryotic ribosomes.
“However, secondary structure downstream of the start codon tend to enhance recognition of start codons by eukaryotic ribosomes [57].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [57]
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- Authors
- Kozak, M.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Kozak, M
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1990-11
- Volume
- 87
- Issue
- 21
- Pages
- 8301-8305
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC54943
- OpenAlex
- W2026487666
- Cited by
- 553
- References
- 1
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 20 · 2023: 20 · 2022: 21 · 2021: 21 · 2020: 20 · 2019: 20 · 2018: 15 · 2017: 22 · 2016: 12 · 2015: 9 · 2014: 14 · 2013: 21 · 2012: 15
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 33915, R01GM033915)
- 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
- AUG codon, ribosome scanning, mRNA secondary structure, 40S ribosome, ribosome stalling, alternative start codons, mRNA leader sequence, eukaryotic translation initiation
- MeSH terms
- Animals, Base Sequence, Calorimetry, Codon, Enhancer Elements, Genetic, Molecular Sequence Data, Nucleic Acid Conformation, Peptide Chain Initiation, Translational, Plasmids, Reticulocytes, Ribosomes, RNA, Messenger, Sequence Homology, Nucleic Acid, Oligonucleotide Probes
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