Initiation of translation in prokaryotes and eukaryotes
Abstract
The mechanisms whereby ribosomes engage a messenger RNA and select the start site for translation differ between prokaryotes and eukaryotes. Initiation sites in polycistronic prokaryotic mRNAs are usually selected via base pairing with ribosomal RNA. That straightforward mechanism is made complicated and interesting by cis- and trans-acting elements employed to regulate translation. Initiation sites in eukaryotic mRNAs are reached via a scanning mechanism which predicts that translation should start at the AUG codon nearest the 5' end of the mRNA. Interest has focused on mechanisms that occasionally allow escape from this first-AUG rule. With natural mRNAs, three escape mechanisms - context-dependent leaky scanning, reinitiation, and possibly direct internal initiation - allow access to AUG codons which, although not first, are still close to the 5' end of the mRNA. This constraint on the initiation step of translation in eukaryotes dictates the location of transcriptional promoters and may have contributed to the evolution of splicing.The binding of Met-tRNA to ribosomes is mediated by a GTP-binding protein in both prokaryotes and eukaryotes, but the more complex structure of the eukaryotic factor (eIF-2) and its association with other proteins underlie some aspects of initiation unique to eukaryotes. Modulation of GTP hydrolysis by eIF-2 is important during the scanning phase of initiation, while modulating the release of GDP from eIF-2 is a key mechanism for regulating tra…
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There is little evidence that +4G and downstream nucleotides contribute to translation initiation.
“There is little evidence that +4G and downstream nucleotides contribute to translation initiation.”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [46]
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 [46]
The -3R has been demonstrated repeatedly to enhance translation initiation.
“First, while the -3R (site 4 in the first column of Table 5) has been demonstrated repeatedly to enhance translation initiation, the effect of +4G (site 10 in Table 5), as well as nucleotides downstream, on translation initiation has been inconclusive [46,49,50,51].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [46]
The effect of +4G and downstream nucleotides on translation initiation has been inconclusive.
“First, while the -3R (site 4 in the first column of Table 5) has been demonstrated repeatedly to enhance translation initiation, the effect of +4G (site 10 in Table 5), as well as nucleotides downstream, on translation initiation has been inconclusive [46,49,50,51].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [46]
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- Authors
- Kozak, M.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Kozak, Marilyn
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 234
- Issue
- 2
- Pages
- 187-208
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W2058426472
- Cited by
- 1,364
- References
- 1
- Citations by year
- 2026: 20 · 2025: 14 · 2024: 21 · 2023: 22 · 2022: 33 · 2021: 34 · 2020: 40 · 2019: 31 · 2018: 41 · 2017: 34 · 2016: 29 · 2015: 28 · 2014: 49 · 2013: 41 · 2012: 34
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene (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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- translation initiation, prokaryotic translation, eukaryotic translation, scanning mechanism, leaky scanning, reinitiation, internal initiation, eIF2, GTP hydrolysis, translation initiation factors, translational regulation, in vitro translation system
- MeSH terms
- Animals, Eukaryotic Cells, Humans, Peptide Chain Initiation, Translational, Prokaryotic Cells, Protein Biosynthesis
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