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Determinants of protein abundance and translation efficiency in S. cerevisiae.

Tuller T, Kupiec M, Ruppin E - PLoS Comput. Biol. (2007)

Bottom Line: It attains a correlation of 0.76 with experimentally determined protein abundance levels on unseen data and successfully cross-predicts protein abundance levels in another yeast species (Schizosaccharomyces pombe).The predicted abundance levels of proteins in known S. cerevisiae complexes, and of interacting proteins, are significantly more coherent than their corresponding mRNA expression levels.Our analysis shows that in parallel to the adaptation occurring at the tRNA level via the codon bias, proteins do undergo a complementary adaptation at the amino acid level to further increase their abundance.

View Article: PubMed Central - PubMed

Affiliation: School of Computer Science, Tel Aviv University, Tel Aviv, Israel. tamirtul@post.tau.ac.il

ABSTRACT
The translation efficiency of most Saccharomyces cerevisiae genes remains fairly constant across poor and rich growth media. This observation has led us to revisit the available data and to examine the potential utility of a protein abundance predictor in reinterpreting existing mRNA expression data. Our predictor is based on large-scale data of mRNA levels, the tRNA adaptation index, and the evolutionary rate. It attains a correlation of 0.76 with experimentally determined protein abundance levels on unseen data and successfully cross-predicts protein abundance levels in another yeast species (Schizosaccharomyces pombe). The predicted abundance levels of proteins in known S. cerevisiae complexes, and of interacting proteins, are significantly more coherent than their corresponding mRNA expression levels. Analysis of gene expression measurement experiments using the predicted protein abundance levels yields new insights that are not readily discernable when clustering the corresponding mRNA expression levels. Comparing protein abundance levels across poor and rich media, we find a general trend for homeostatic regulation where transcription and translation change in a reciprocal manner. This phenomenon is more prominent near origins of replications. Our analysis shows that in parallel to the adaptation occurring at the tRNA level via the codon bias, proteins do undergo a complementary adaptation at the amino acid level to further increase their abundance.

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Partial Correlations between the Frequencies of Amino Acids Composing a Protein and Its Abundance Level (after Controlling for the Effect of tAI)
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pcbi-0030248-g003: Partial Correlations between the Frequencies of Amino Acids Composing a Protein and Its Abundance Level (after Controlling for the Effect of tAI)

Mentions: Like previous studies [4,26], we have also found a significant correlation between the abundance of a particular protein and the frequency of certain amino acids composing it, the most prominent being alanine and valine (positive correlation), and serine and aspargine (negative correlation; Figure S1). This observation has been previously attributed to the different values of the tAI (or the CAI) of these amino acids, which can modulate translation efficiency [16,17]. However, we find that even after controlling for the effect of their different tAIs, the frequency of these amino acids remains significantly correlated with protein abundance, and their frequency at abundant proteins remains highly significant (see partial correlations reported in Figure 3, and similar results after controlling for CAI in Figure S2). The Spearman rank correlation of amino acid frequencies and protein abundance remains significant even after additionally controlling for the effect of mRNA expression levels (Table S7). This finding suggests that in parallel to the adaptation occurring at the tRNA level via the codon bias [27,28], proteins do undergo a complementary adaptation at the amino acid level via amino acid substitution to further increase their protein abundance. The small, neutral, and nonpolar amino acid alanine is probably ideally suited for this putative substitute role, given its known neutral effect on protein stability [29]. Both alanine and valine are present at relatively high concentrations within the yeast cell, and their corresponding acyl-tRNA synthases are also expressed at high levels (Table S8), aiding in their efficient incorporation during transcription (however, adding frequencies of amino acids to our predictor did not improve its performance significantly; see Text S6).


Determinants of protein abundance and translation efficiency in S. cerevisiae.

Tuller T, Kupiec M, Ruppin E - PLoS Comput. Biol. (2007)

Partial Correlations between the Frequencies of Amino Acids Composing a Protein and Its Abundance Level (after Controlling for the Effect of tAI)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230678&req=5

pcbi-0030248-g003: Partial Correlations between the Frequencies of Amino Acids Composing a Protein and Its Abundance Level (after Controlling for the Effect of tAI)
Mentions: Like previous studies [4,26], we have also found a significant correlation between the abundance of a particular protein and the frequency of certain amino acids composing it, the most prominent being alanine and valine (positive correlation), and serine and aspargine (negative correlation; Figure S1). This observation has been previously attributed to the different values of the tAI (or the CAI) of these amino acids, which can modulate translation efficiency [16,17]. However, we find that even after controlling for the effect of their different tAIs, the frequency of these amino acids remains significantly correlated with protein abundance, and their frequency at abundant proteins remains highly significant (see partial correlations reported in Figure 3, and similar results after controlling for CAI in Figure S2). The Spearman rank correlation of amino acid frequencies and protein abundance remains significant even after additionally controlling for the effect of mRNA expression levels (Table S7). This finding suggests that in parallel to the adaptation occurring at the tRNA level via the codon bias [27,28], proteins do undergo a complementary adaptation at the amino acid level via amino acid substitution to further increase their protein abundance. The small, neutral, and nonpolar amino acid alanine is probably ideally suited for this putative substitute role, given its known neutral effect on protein stability [29]. Both alanine and valine are present at relatively high concentrations within the yeast cell, and their corresponding acyl-tRNA synthases are also expressed at high levels (Table S8), aiding in their efficient incorporation during transcription (however, adding frequencies of amino acids to our predictor did not improve its performance significantly; see Text S6).

Bottom Line: It attains a correlation of 0.76 with experimentally determined protein abundance levels on unseen data and successfully cross-predicts protein abundance levels in another yeast species (Schizosaccharomyces pombe).The predicted abundance levels of proteins in known S. cerevisiae complexes, and of interacting proteins, are significantly more coherent than their corresponding mRNA expression levels.Our analysis shows that in parallel to the adaptation occurring at the tRNA level via the codon bias, proteins do undergo a complementary adaptation at the amino acid level to further increase their abundance.

View Article: PubMed Central - PubMed

Affiliation: School of Computer Science, Tel Aviv University, Tel Aviv, Israel. tamirtul@post.tau.ac.il

ABSTRACT
The translation efficiency of most Saccharomyces cerevisiae genes remains fairly constant across poor and rich growth media. This observation has led us to revisit the available data and to examine the potential utility of a protein abundance predictor in reinterpreting existing mRNA expression data. Our predictor is based on large-scale data of mRNA levels, the tRNA adaptation index, and the evolutionary rate. It attains a correlation of 0.76 with experimentally determined protein abundance levels on unseen data and successfully cross-predicts protein abundance levels in another yeast species (Schizosaccharomyces pombe). The predicted abundance levels of proteins in known S. cerevisiae complexes, and of interacting proteins, are significantly more coherent than their corresponding mRNA expression levels. Analysis of gene expression measurement experiments using the predicted protein abundance levels yields new insights that are not readily discernable when clustering the corresponding mRNA expression levels. Comparing protein abundance levels across poor and rich media, we find a general trend for homeostatic regulation where transcription and translation change in a reciprocal manner. This phenomenon is more prominent near origins of replications. Our analysis shows that in parallel to the adaptation occurring at the tRNA level via the codon bias, proteins do undergo a complementary adaptation at the amino acid level to further increase their abundance.

Show MeSH