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Coupled evolution of transcription and mRNA degradation.

Dori-Bachash M, Shema E, Tirosh I - PLoS Biol. (2011)

Bottom Line: Surprisingly, we find that around half of the evolutionary changes in mRNA degradation were coupled to transcriptional changes that exert opposite effects on mRNA levels.Coupled changes are associated with divergence of two complexes that were previously implicated both in transcription and in mRNA degradation (Rpb4/7 and Ccr4-Not), as well as with sequence divergence of transcription factor binding motifs.These results suggest that an opposite coupling between the regulation of transcription and that of mRNA degradation has shaped the evolution of gene regulation in yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
mRNA levels are determined by the balance between transcription and mRNA degradation, and while transcription has been extensively studied, very little is known regarding the regulation of mRNA degradation and its coordination with transcription. Here we examine the evolution of mRNA degradation rates between two closely related yeast species. Surprisingly, we find that around half of the evolutionary changes in mRNA degradation were coupled to transcriptional changes that exert opposite effects on mRNA levels. Analysis of mRNA degradation rates in an interspecific hybrid further suggests that opposite evolutionary changes in transcription and in mRNA degradation are mechanistically coupled and were generated by the same individual mutations. Coupled changes are associated with divergence of two complexes that were previously implicated both in transcription and in mRNA degradation (Rpb4/7 and Ccr4-Not), as well as with sequence divergence of transcription factor binding motifs. These results suggest that an opposite coupling between the regulation of transcription and that of mRNA degradation has shaped the evolution of gene regulation in yeast.

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Large-scale analysis of mRNA degradation rates in two yeast species.(a) R2 values (goodness-of-fit) for a linear-fit to the log2 mRNA levels at the four time points (see inset for example of a single gene). As control, we performed the same analysis to 10,000 shuffled profiles in which each time-point is taken from a different gene (randomly selected), thus retaining the overall degradation of mRNA levels but shuffling the gene-specific degradation rates. 78% of the real profiles (compared with 18% of the shuffled profiles) obtained an R2 value above 0.94 and were included in all further analyses. (b) Correlation of S. cerevisiae (blue) and S. paradoxus (red) mRNA degradation rates: (i) between different probes for the same genes (note that different probes typically have different hybridization intensities, yet the mRNA degradation rates are highly reproducible, see Materials and Methods), (ii) between biological repeat experiments, and (iii) between this work and a previous work that used a temperature-sensitive mutation in RNA polymerase II to block transcription. Note that although this previous work analyzed only S. cerevisiae, it has high correlations with our data for the two species. (c) Scatter-plot of mRNA degradation rates in S. cerevisiae and S. paradoxus, which have a genome-wide correlation of 0.78. (d) Patterns of mRNA degradation for the 12 oxidative phosphorylation genes included in the analysis in S. cerevisiae (blue) and S. paradoxus (red).
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pbio-1001106-g001: Large-scale analysis of mRNA degradation rates in two yeast species.(a) R2 values (goodness-of-fit) for a linear-fit to the log2 mRNA levels at the four time points (see inset for example of a single gene). As control, we performed the same analysis to 10,000 shuffled profiles in which each time-point is taken from a different gene (randomly selected), thus retaining the overall degradation of mRNA levels but shuffling the gene-specific degradation rates. 78% of the real profiles (compared with 18% of the shuffled profiles) obtained an R2 value above 0.94 and were included in all further analyses. (b) Correlation of S. cerevisiae (blue) and S. paradoxus (red) mRNA degradation rates: (i) between different probes for the same genes (note that different probes typically have different hybridization intensities, yet the mRNA degradation rates are highly reproducible, see Materials and Methods), (ii) between biological repeat experiments, and (iii) between this work and a previous work that used a temperature-sensitive mutation in RNA polymerase II to block transcription. Note that although this previous work analyzed only S. cerevisiae, it has high correlations with our data for the two species. (c) Scatter-plot of mRNA degradation rates in S. cerevisiae and S. paradoxus, which have a genome-wide correlation of 0.78. (d) Patterns of mRNA degradation for the 12 oxidative phosphorylation genes included in the analysis in S. cerevisiae (blue) and S. paradoxus (red).

Mentions: To compare the mRNA degradation rates of the two species, we monitored mRNA levels following transcriptional arrest using 1,10-Phenantroline [7],[26]. mRNA levels were measured at 0, 20, 40, and 60 min after addition of the drug using a two-species microarray [25]. As expected, the profiles of most genes were well approximated by an exponential decay, which is reflected by a linear decrease of the log2 mRNA levels with time (Figure 1a). Degradation rates were estimated as the slope of the linear fit for 78% of the genes that had an R2 value (goodness-of-fit) above 0.94, while genes with lower R2 were excluded from further analysis. The calculated mRNA degradation rates of S. cerevisiae genes were highly reproducible among two biological repeats and between probes that were designed for different positions of the same genes, and were consistent with previous measurements of mRNA degradation that utilized a PolII mutant strain to block transcription (Figure 1b) [24].


Coupled evolution of transcription and mRNA degradation.

Dori-Bachash M, Shema E, Tirosh I - PLoS Biol. (2011)

Large-scale analysis of mRNA degradation rates in two yeast species.(a) R2 values (goodness-of-fit) for a linear-fit to the log2 mRNA levels at the four time points (see inset for example of a single gene). As control, we performed the same analysis to 10,000 shuffled profiles in which each time-point is taken from a different gene (randomly selected), thus retaining the overall degradation of mRNA levels but shuffling the gene-specific degradation rates. 78% of the real profiles (compared with 18% of the shuffled profiles) obtained an R2 value above 0.94 and were included in all further analyses. (b) Correlation of S. cerevisiae (blue) and S. paradoxus (red) mRNA degradation rates: (i) between different probes for the same genes (note that different probes typically have different hybridization intensities, yet the mRNA degradation rates are highly reproducible, see Materials and Methods), (ii) between biological repeat experiments, and (iii) between this work and a previous work that used a temperature-sensitive mutation in RNA polymerase II to block transcription. Note that although this previous work analyzed only S. cerevisiae, it has high correlations with our data for the two species. (c) Scatter-plot of mRNA degradation rates in S. cerevisiae and S. paradoxus, which have a genome-wide correlation of 0.78. (d) Patterns of mRNA degradation for the 12 oxidative phosphorylation genes included in the analysis in S. cerevisiae (blue) and S. paradoxus (red).
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pbio-1001106-g001: Large-scale analysis of mRNA degradation rates in two yeast species.(a) R2 values (goodness-of-fit) for a linear-fit to the log2 mRNA levels at the four time points (see inset for example of a single gene). As control, we performed the same analysis to 10,000 shuffled profiles in which each time-point is taken from a different gene (randomly selected), thus retaining the overall degradation of mRNA levels but shuffling the gene-specific degradation rates. 78% of the real profiles (compared with 18% of the shuffled profiles) obtained an R2 value above 0.94 and were included in all further analyses. (b) Correlation of S. cerevisiae (blue) and S. paradoxus (red) mRNA degradation rates: (i) between different probes for the same genes (note that different probes typically have different hybridization intensities, yet the mRNA degradation rates are highly reproducible, see Materials and Methods), (ii) between biological repeat experiments, and (iii) between this work and a previous work that used a temperature-sensitive mutation in RNA polymerase II to block transcription. Note that although this previous work analyzed only S. cerevisiae, it has high correlations with our data for the two species. (c) Scatter-plot of mRNA degradation rates in S. cerevisiae and S. paradoxus, which have a genome-wide correlation of 0.78. (d) Patterns of mRNA degradation for the 12 oxidative phosphorylation genes included in the analysis in S. cerevisiae (blue) and S. paradoxus (red).
Mentions: To compare the mRNA degradation rates of the two species, we monitored mRNA levels following transcriptional arrest using 1,10-Phenantroline [7],[26]. mRNA levels were measured at 0, 20, 40, and 60 min after addition of the drug using a two-species microarray [25]. As expected, the profiles of most genes were well approximated by an exponential decay, which is reflected by a linear decrease of the log2 mRNA levels with time (Figure 1a). Degradation rates were estimated as the slope of the linear fit for 78% of the genes that had an R2 value (goodness-of-fit) above 0.94, while genes with lower R2 were excluded from further analysis. The calculated mRNA degradation rates of S. cerevisiae genes were highly reproducible among two biological repeats and between probes that were designed for different positions of the same genes, and were consistent with previous measurements of mRNA degradation that utilized a PolII mutant strain to block transcription (Figure 1b) [24].

Bottom Line: Surprisingly, we find that around half of the evolutionary changes in mRNA degradation were coupled to transcriptional changes that exert opposite effects on mRNA levels.Coupled changes are associated with divergence of two complexes that were previously implicated both in transcription and in mRNA degradation (Rpb4/7 and Ccr4-Not), as well as with sequence divergence of transcription factor binding motifs.These results suggest that an opposite coupling between the regulation of transcription and that of mRNA degradation has shaped the evolution of gene regulation in yeast.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
mRNA levels are determined by the balance between transcription and mRNA degradation, and while transcription has been extensively studied, very little is known regarding the regulation of mRNA degradation and its coordination with transcription. Here we examine the evolution of mRNA degradation rates between two closely related yeast species. Surprisingly, we find that around half of the evolutionary changes in mRNA degradation were coupled to transcriptional changes that exert opposite effects on mRNA levels. Analysis of mRNA degradation rates in an interspecific hybrid further suggests that opposite evolutionary changes in transcription and in mRNA degradation are mechanistically coupled and were generated by the same individual mutations. Coupled changes are associated with divergence of two complexes that were previously implicated both in transcription and in mRNA degradation (Rpb4/7 and Ccr4-Not), as well as with sequence divergence of transcription factor binding motifs. These results suggest that an opposite coupling between the regulation of transcription and that of mRNA degradation has shaped the evolution of gene regulation in yeast.

Show MeSH