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

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 experimen...

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Autor principal: Xia, Xuhua
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781341/
https://www.ncbi.nlm.nih.gov/pubmed/17285142
http://dx.doi.org/10.1371/journal.pone.0000188
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author Xia, Xuhua
author_facet Xia, Xuhua
author_sort Xia, Xuhua
collection PubMed
description 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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spelling pubmed-17813412007-02-07 The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation Xia, Xuhua PLoS One Research Article 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. Public Library of Science 2007-02-07 /pmc/articles/PMC1781341/ /pubmed/17285142 http://dx.doi.org/10.1371/journal.pone.0000188 Text en Xuhua Xia. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xia, Xuhua
The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title_full The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title_fullStr The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title_full_unstemmed The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title_short The +4G Site in Kozak Consensus Is Not Related to the Efficiency of Translation Initiation
title_sort +4g site in kozak consensus is not related to the efficiency of translation initiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781341/
https://www.ncbi.nlm.nih.gov/pubmed/17285142
http://dx.doi.org/10.1371/journal.pone.0000188
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