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Cited by 45RNA and protein synthesis mechanismsGenomics and Phylogenetic StudiesRNA Research and Splicing

The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation

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Xia, Xuhua·2007·PLoS ONE
DOI 10.1371/journal.pone.0000188PMC PMC1781341
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Abstract

The optimal context for translation initiation in mammalian species is GCCRCCaugG (where R = purine and "aug" is the initiation codon), with the -3R and +4G being particularly important. The presence of +4G has been interpreted as necessary for efficient translation initiation. Accumulated experimental and bioinformatic evidence has suggested an alternative explanation based on amino acid constraint on the second codon, i.e., amino acid Ala or Gly are needed as the second amino acid in the nascent peptide for the cleavage of the initiator Met, and the consequent overuse of Ala and Gly codons (GCN and GGN) leads to the +4G consensus. I performed a critical test of these alternative hypotheses on +4G based on 34169 human protein-coding genes and published gene expression data. The result shows that the prevalence of +4G is not related to translation initiation. Among the five G-starting codons, only alanine codons (GCN), and glycine codons (GGN) to a much smaller extent, are overrepresented at the second codon, whereas the other three codons are not overrepresented. While highly expressed genes have more +4G than lowly expressed genes, the difference is caused by GCN and GGN codons at the second codon. These results are inconsistent with +4G being needed for efficient translation initiation, but consistent with the proposal of amino acid constraint hypothesis.

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  • N-terminal methionine excision requires a small and nonpolar amino acid such as alanine and glycine.

    “About 60% of the proteins experience N-terminal methionine excision (NME) which requires a small and nonpolar amino acid such as alanine and glycine.”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [53]

    The Introduction says initiator-methionine removal is most efficient when the second amino acid is small, and identifies alanine and glycine as the two smallest. But the Discussion says cleavage also occurs with valine at that position, so the claim overstates this preference as a requirement. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • About 60% of proteins experience N-terminal methionine excision (NME).

    “About 60% of the proteins experience N-terminal methionine excision (NME) which requires a small and nonpolar amino acid such as alanine and glycine.”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [53]

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Authors
Xia, X.
Affiliations
University of Ottawa (CA)
Corresponding author
Xia, Xuhua
ORCID
Xia, Xuhua
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2007-02-07
Volume
2
Issue
2
Pages
e188
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0000188
PMC
PMC1781341
OpenAlex
W1969207770
Cited by
45
References
1
Citations by year
2026: 1 · 2024: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 8 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 4
FWCI
1.11
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
translation initiation, gene expression, human protein-coding genes, codon usage
MeSH terms
Alanine, Codon, Gene Expression Regulation, Glycine, Humans, Models, Genetic, Ribosomes, Protein Biosynthesis, Consensus Sequence

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