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Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate.

Gorochowski TE, Ignatova Z, Bovenberg RA, Roubos JA - Nucleic Acids Res. (2015)

Bottom Line: Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency.Here we provide evidence that this results from an inherent trade-off between these factors.The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.

View Article: PubMed Central - PubMed

Affiliation: DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands teg@mit.edu.

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Codon usage for protein coding regions of mRNAs with high and low mRNA secondary structure across the Saccharomyces cerevisiae and Escherichia coli genomes. Separate plots are displayed for each amino acid, with upper plots (red) showing regions with high mRNA secondary structure and lower plots (blue) regions with low mRNA secondary structure. Each plot displays the normalized usage of each codon for the associated amino acid on a scale from 0 to 0.08 and codons are sorted from left to right in terms of predicted translational times, see Supplementary Table S1 (stop codons are excluded), fastest (left) to slowest (right). Notice a clear bias toward faster codons in regions with high secondary structure that is not always related to G/C content in the second and third positions (e.g. in S. cerevisiae see the CCA codon for proline and GAA codon for glutamic acid, both of which display a strong bias in highly structured regions even though other synonymous codons with greater G/C content exist they are, however, predicted to be the fastest translated). Horizontal grid lines are positioned at intervals of 0.01. Number in top left corner of each plot denotes the percentage of individual codons shown in the plot in relation to the total number of codons contained within the total associated low or high mRNA secondary structure regions. For example in E. coli, codons coding for alanine in low secondary structure regions correspond to 6.6% of all codons in low structured regions, while the same codons in high secondary structure regions correspond to 13.7% of all codons in high structured regions.
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Figure 4: Codon usage for protein coding regions of mRNAs with high and low mRNA secondary structure across the Saccharomyces cerevisiae and Escherichia coli genomes. Separate plots are displayed for each amino acid, with upper plots (red) showing regions with high mRNA secondary structure and lower plots (blue) regions with low mRNA secondary structure. Each plot displays the normalized usage of each codon for the associated amino acid on a scale from 0 to 0.08 and codons are sorted from left to right in terms of predicted translational times, see Supplementary Table S1 (stop codons are excluded), fastest (left) to slowest (right). Notice a clear bias toward faster codons in regions with high secondary structure that is not always related to G/C content in the second and third positions (e.g. in S. cerevisiae see the CCA codon for proline and GAA codon for glutamic acid, both of which display a strong bias in highly structured regions even though other synonymous codons with greater G/C content exist they are, however, predicted to be the fastest translated). Horizontal grid lines are positioned at intervals of 0.01. Number in top left corner of each plot denotes the percentage of individual codons shown in the plot in relation to the total number of codons contained within the total associated low or high mRNA secondary structure regions. For example in E. coli, codons coding for alanine in low secondary structure regions correspond to 6.6% of all codons in low structured regions, while the same codons in high secondary structure regions correspond to 13.7% of all codons in high structured regions.

Mentions: Finally we assessed the amino acid composition of high and low structured regions (Supplementary Figure S4). We found a slight enrichment of some amino acids in high or low structured regions. Alanine was commonly found in high structured regions and lysine, asparagine, phenylalanine and isoleucine in low structured regions across both organisms. This may be partially due to the sequences of the codons encoding each amino acid. For example, amino acids found in high-structured regions are coded for by codons that are G/C rich, while amino acids found in low-structured regions are coded for by A/T rich codons (FigureĀ 4).


Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate.

Gorochowski TE, Ignatova Z, Bovenberg RA, Roubos JA - Nucleic Acids Res. (2015)

Codon usage for protein coding regions of mRNAs with high and low mRNA secondary structure across the Saccharomyces cerevisiae and Escherichia coli genomes. Separate plots are displayed for each amino acid, with upper plots (red) showing regions with high mRNA secondary structure and lower plots (blue) regions with low mRNA secondary structure. Each plot displays the normalized usage of each codon for the associated amino acid on a scale from 0 to 0.08 and codons are sorted from left to right in terms of predicted translational times, see Supplementary Table S1 (stop codons are excluded), fastest (left) to slowest (right). Notice a clear bias toward faster codons in regions with high secondary structure that is not always related to G/C content in the second and third positions (e.g. in S. cerevisiae see the CCA codon for proline and GAA codon for glutamic acid, both of which display a strong bias in highly structured regions even though other synonymous codons with greater G/C content exist they are, however, predicted to be the fastest translated). Horizontal grid lines are positioned at intervals of 0.01. Number in top left corner of each plot denotes the percentage of individual codons shown in the plot in relation to the total number of codons contained within the total associated low or high mRNA secondary structure regions. For example in E. coli, codons coding for alanine in low secondary structure regions correspond to 6.6% of all codons in low structured regions, while the same codons in high secondary structure regions correspond to 13.7% of all codons in high structured regions.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 4: Codon usage for protein coding regions of mRNAs with high and low mRNA secondary structure across the Saccharomyces cerevisiae and Escherichia coli genomes. Separate plots are displayed for each amino acid, with upper plots (red) showing regions with high mRNA secondary structure and lower plots (blue) regions with low mRNA secondary structure. Each plot displays the normalized usage of each codon for the associated amino acid on a scale from 0 to 0.08 and codons are sorted from left to right in terms of predicted translational times, see Supplementary Table S1 (stop codons are excluded), fastest (left) to slowest (right). Notice a clear bias toward faster codons in regions with high secondary structure that is not always related to G/C content in the second and third positions (e.g. in S. cerevisiae see the CCA codon for proline and GAA codon for glutamic acid, both of which display a strong bias in highly structured regions even though other synonymous codons with greater G/C content exist they are, however, predicted to be the fastest translated). Horizontal grid lines are positioned at intervals of 0.01. Number in top left corner of each plot denotes the percentage of individual codons shown in the plot in relation to the total number of codons contained within the total associated low or high mRNA secondary structure regions. For example in E. coli, codons coding for alanine in low secondary structure regions correspond to 6.6% of all codons in low structured regions, while the same codons in high secondary structure regions correspond to 13.7% of all codons in high structured regions.
Mentions: Finally we assessed the amino acid composition of high and low structured regions (Supplementary Figure S4). We found a slight enrichment of some amino acids in high or low structured regions. Alanine was commonly found in high structured regions and lysine, asparagine, phenylalanine and isoleucine in low structured regions across both organisms. This may be partially due to the sequences of the codons encoding each amino acid. For example, amino acids found in high-structured regions are coded for by codons that are G/C rich, while amino acids found in low-structured regions are coded for by A/T rich codons (FigureĀ 4).

Bottom Line: Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency.Here we provide evidence that this results from an inherent trade-off between these factors.The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.

View Article: PubMed Central - PubMed

Affiliation: DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands teg@mit.edu.

Show MeSH
Related in: MedlinePlus