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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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Distribution of TE and RTE in S. cerevisiae(A) Top: S. cerevisiae genes sorted by their TE (log scale) in YEPD (rich) medium. A large variability of TE values (more than six orders of magnitude) is observed. Bottom: histogram, mean, and variance of TE in YEPD.(B) Top: S. cerevisiae genes sorted by their TE (log scale) in SD (poor) medium. A similar large variability of TE values is seen. Bottom: histogram, mean, and variance of TE in SD.(C) Top: S. cerevisiae genes sorted by the log-ratio of their TEs [RTE = (pSD/mSD)/(pYEPD/mYEPD)] in SD versus YEPD (log scale). A total of 91% of the genes have an RTE value between 0.5 and 2. Bottom: histogram, mean, and variance of RTE.
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pcbi-0030248-g001: Distribution of TE and RTE in S. cerevisiae(A) Top: S. cerevisiae genes sorted by their TE (log scale) in YEPD (rich) medium. A large variability of TE values (more than six orders of magnitude) is observed. Bottom: histogram, mean, and variance of TE in YEPD.(B) Top: S. cerevisiae genes sorted by their TE (log scale) in SD (poor) medium. A similar large variability of TE values is seen. Bottom: histogram, mean, and variance of TE in SD.(C) Top: S. cerevisiae genes sorted by the log-ratio of their TEs [RTE = (pSD/mSD)/(pYEPD/mYEPD)] in SD versus YEPD (log scale). A total of 91% of the genes have an RTE value between 0.5 and 2. Bottom: histogram, mean, and variance of RTE.

Mentions: Genome-wide studies have measured mRNA and protein levels in the yeast Saccharomyces cerevisiae growing either in rich medium (yeast extract, peptone, and dextrose [YEPD]) or on poor, defined medium (synthetic dextrose [SD]) [2,3,5]. When protein abundance is compared to the corresponding mRNA levels in a given medium, the translation efficiency (TE), i.e., the ratio between protein abundance and mRNA levels, exhibits a large variability among genes (spanning across six orders of magnitude; Figure 1A and 1B). However, when the TEs of a given protein are compared across the two different growth conditions, notably very little variation is observed (Figure 1C): the ratios between the TEs of most proteins in the two conditions are close to 1, with >90% of the proteins showing a ratio between 0.5 and 2. This observation, albeit currently limited to the two types of media for which genome-wide data are available, suggests that the efficiency of translation per mRNA molecule of many genes may be largely invariable under different conditions. This fairly constant TE of yeast genes has motivated us to create a large-scale predictor of protein abundance, with the aim of studying its utility for inferring protein abundance levels across different conditions.


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

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

Distribution of TE and RTE in S. cerevisiae(A) Top: S. cerevisiae genes sorted by their TE (log scale) in YEPD (rich) medium. A large variability of TE values (more than six orders of magnitude) is observed. Bottom: histogram, mean, and variance of TE in YEPD.(B) Top: S. cerevisiae genes sorted by their TE (log scale) in SD (poor) medium. A similar large variability of TE values is seen. Bottom: histogram, mean, and variance of TE in SD.(C) Top: S. cerevisiae genes sorted by the log-ratio of their TEs [RTE = (pSD/mSD)/(pYEPD/mYEPD)] in SD versus YEPD (log scale). A total of 91% of the genes have an RTE value between 0.5 and 2. Bottom: histogram, mean, and variance of RTE.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2230678&req=5

pcbi-0030248-g001: Distribution of TE and RTE in S. cerevisiae(A) Top: S. cerevisiae genes sorted by their TE (log scale) in YEPD (rich) medium. A large variability of TE values (more than six orders of magnitude) is observed. Bottom: histogram, mean, and variance of TE in YEPD.(B) Top: S. cerevisiae genes sorted by their TE (log scale) in SD (poor) medium. A similar large variability of TE values is seen. Bottom: histogram, mean, and variance of TE in SD.(C) Top: S. cerevisiae genes sorted by the log-ratio of their TEs [RTE = (pSD/mSD)/(pYEPD/mYEPD)] in SD versus YEPD (log scale). A total of 91% of the genes have an RTE value between 0.5 and 2. Bottom: histogram, mean, and variance of RTE.
Mentions: Genome-wide studies have measured mRNA and protein levels in the yeast Saccharomyces cerevisiae growing either in rich medium (yeast extract, peptone, and dextrose [YEPD]) or on poor, defined medium (synthetic dextrose [SD]) [2,3,5]. When protein abundance is compared to the corresponding mRNA levels in a given medium, the translation efficiency (TE), i.e., the ratio between protein abundance and mRNA levels, exhibits a large variability among genes (spanning across six orders of magnitude; Figure 1A and 1B). However, when the TEs of a given protein are compared across the two different growth conditions, notably very little variation is observed (Figure 1C): the ratios between the TEs of most proteins in the two conditions are close to 1, with >90% of the proteins showing a ratio between 0.5 and 2. This observation, albeit currently limited to the two types of media for which genome-wide data are available, suggests that the efficiency of translation per mRNA molecule of many genes may be largely invariable under different conditions. This fairly constant TE of yeast genes has motivated us to create a large-scale predictor of protein abundance, with the aim of studying its utility for inferring protein abundance levels across different conditions.

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