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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.

Show MeSH
The Distribution of Genes with High RTEs at Different Distances from Origins of ReplicationThe distribution of genes with high RTE (RTE > 2.5), and distribution of all genes at different distances from origins of replication. The number of genes with high RTE is 49; the total number of genes studied is 2,200. The number of genes with high RTE that are located within 1 kbp from an ARS is statistically significant using a hyper-geometric text (p < 0.05).
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pcbi-0030248-g004: The Distribution of Genes with High RTEs at Different Distances from Origins of ReplicationThe distribution of genes with high RTE (RTE > 2.5), and distribution of all genes at different distances from origins of replication. The number of genes with high RTE is 49; the total number of genes studied is 2,200. The number of genes with high RTE that are located within 1 kbp from an ARS is statistically significant using a hyper-geometric text (p < 0.05).

Mentions: The group of genes exhibiting extremely high RTE levels is enriched for mitochondrial genes (21/48 are mitochondrial genes; chi-square p = 10−16), with many of these genes being related to mitochondrial biosynthesis and metabolism. Thus, the increase in the level of mitochondrial proteins, reflecting the need for higher-yield energy production in poor growth conditions, is achieved mainly by boosting translation efficiency. Interestingly, the high RTE group is also enriched with genes that map very close to origins of replication (autonomously replicating sequence [ARS]), including four genes abutting at the origin of replication (out of a total of 24 genes with a similar location in the yeast genome, providing a chi-square p = 1.1 × 10−6), and twice the expected number of genes located within 1 kbp from an ARS (p < 0.05; see Figure 4). A possible explanation for this intriguing connection is that the replication machinery, when binding to origins of replication, attenuates transcription, either by steric hindrance or by competition for DNA binding [30]. This interference is then compensated in turn by higher translation efficiency and a more flexible regulation of translation, as reflected by its high RTE levels. Indeed, the average mSD /mYEPD ratios of genes that have extremely high RTE and that are less than 1 kb from an ARS is only 0.8. One putative mechanism that may underlie this intriguing phenomenon is that certain proteins that participate in replication and transcription (e.g., Rap1 and Abs1) could be incorporated into the mRNA, exported from the nucleus, and differentially affect the rate of translation at the ribosome. Similar mechanisms have been suggested for the activity of proteins such as Yra1, Sub2, and the THO complex, which affect transcription, splicing efficiency, and nuclear export [31].


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

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

The Distribution of Genes with High RTEs at Different Distances from Origins of ReplicationThe distribution of genes with high RTE (RTE > 2.5), and distribution of all genes at different distances from origins of replication. The number of genes with high RTE is 49; the total number of genes studied is 2,200. The number of genes with high RTE that are located within 1 kbp from an ARS is statistically significant using a hyper-geometric text (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-0030248-g004: The Distribution of Genes with High RTEs at Different Distances from Origins of ReplicationThe distribution of genes with high RTE (RTE > 2.5), and distribution of all genes at different distances from origins of replication. The number of genes with high RTE is 49; the total number of genes studied is 2,200. The number of genes with high RTE that are located within 1 kbp from an ARS is statistically significant using a hyper-geometric text (p < 0.05).
Mentions: The group of genes exhibiting extremely high RTE levels is enriched for mitochondrial genes (21/48 are mitochondrial genes; chi-square p = 10−16), with many of these genes being related to mitochondrial biosynthesis and metabolism. Thus, the increase in the level of mitochondrial proteins, reflecting the need for higher-yield energy production in poor growth conditions, is achieved mainly by boosting translation efficiency. Interestingly, the high RTE group is also enriched with genes that map very close to origins of replication (autonomously replicating sequence [ARS]), including four genes abutting at the origin of replication (out of a total of 24 genes with a similar location in the yeast genome, providing a chi-square p = 1.1 × 10−6), and twice the expected number of genes located within 1 kbp from an ARS (p < 0.05; see Figure 4). A possible explanation for this intriguing connection is that the replication machinery, when binding to origins of replication, attenuates transcription, either by steric hindrance or by competition for DNA binding [30]. This interference is then compensated in turn by higher translation efficiency and a more flexible regulation of translation, as reflected by its high RTE levels. Indeed, the average mSD /mYEPD ratios of genes that have extremely high RTE and that are less than 1 kb from an ARS is only 0.8. One putative mechanism that may underlie this intriguing phenomenon is that certain proteins that participate in replication and transcription (e.g., Rap1 and Abs1) could be incorporated into the mRNA, exported from the nucleus, and differentially affect the rate of translation at the ribosome. Similar mechanisms have been suggested for the activity of proteins such as Yra1, Sub2, and the THO complex, which affect transcription, splicing efficiency, and nuclear export [31].

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