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Uncovering genes with divergent mRNA-protein dynamics in Streptomyces coelicolor.

Jayapal KP, Philp RJ, Kok YJ, Yap MG, Sherman DH, Griffin TJ, Hu WS - PLoS ONE (2008)

Bottom Line: Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels.Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends.Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.

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Related in: MedlinePlus

Examples of related genes displaying similar behavior.Examples of functionally or chromosomally clustered genes exhibiting discordant mRNA and protein dynamics trends as identified using PCA. Dashed lines indicate regions where data interpolation was performed for PCA calculations.
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pone-0002097-g006: Examples of related genes displaying similar behavior.Examples of functionally or chromosomally clustered genes exhibiting discordant mRNA and protein dynamics trends as identified using PCA. Dashed lines indicate regions where data interpolation was performed for PCA calculations.

Mentions: Integrating transcriptome and proteome data with available functional information yields valuable biological insights. A careful examination of Figure 5 reveals that several mRNA and proteins are regulated at a pathway or sub-pathway level. It is evident that, in a number of cases, even when dissonant trends are observed between mRNA and protein profiles (discovered using PCA), such behaviors are usually conserved across at least a few functionally related and/or chromosomally linked genes. Figure 6 shows some interesting profiles that fall in this category. Surprisingly certain groups of genes exhibited not just discordant, but contrasting mRNA-protein profiles. These include a putative protein secretion system (SCO1515–1517; Figure 6A), a glutamate uptake system (GluABCD, SCO5774–77; Figure 6B) and a xylose uptake system (SCO6008–6011; Figure 6C). In each case, the proteins exhibited a two- to eight-fold increase in abundance upon entry into stationary phase while the corresponding transcripts displayed a concomitant two- to four-fold down-regulation. Another set of genes is comprised of those for which the protein levels remained relatively constant while mRNA amounts decreased rapidly in stationary phase, hinting at lower rates of protein turnover than mRNA. These include RNA polymerase subunits (RpoBC, SCO4654/55; Figure 6D), phosphoribosyl transferases/ribosomal proteins (SCO3122–24; Figure 6E), a set of ABC transporters (BkdBC, SCO5113/14; Figure 6F), ATP synthase subunits (AtpABC, SCO5367/71/74; Figure 6G), a set of chromosomally linked hypothetical proteins (SCO1651/1655, Figure 6H) and succinate dehydrogenase subunits (DhsAB, SCO4855/56; Figure 6I). Several other distinct profiles were also observed including cases where mRNA was transiently up-regulated but subsequently down-regulated while protein levels remained constant (Figure 6K and 6L) or displayed an increase during transition to stationary phase (Figure 6J). However, the most common type of divergent behavior was differing degrees of differential patterns in largely the same direction. Four such examples are shown in Figure 6 – a set of arginine biosynthesis genes (SCO1222–23; Figure 6M; up-regulated), oxidative stress response genes (AhpCD, SCO5031–32; Figure 6N; down-regulated), fatty acid biosynthesis genes (FabDHF, SCO2387/88/90; Figure 6O; down-regulated) and two other chromosomally linked proteins (DNA-binding protein Hu and malate oxidoreductase, SCO2950/51; Figure 6P).


Uncovering genes with divergent mRNA-protein dynamics in Streptomyces coelicolor.

Jayapal KP, Philp RJ, Kok YJ, Yap MG, Sherman DH, Griffin TJ, Hu WS - PLoS ONE (2008)

Examples of related genes displaying similar behavior.Examples of functionally or chromosomally clustered genes exhibiting discordant mRNA and protein dynamics trends as identified using PCA. Dashed lines indicate regions where data interpolation was performed for PCA calculations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2367054&req=5

pone-0002097-g006: Examples of related genes displaying similar behavior.Examples of functionally or chromosomally clustered genes exhibiting discordant mRNA and protein dynamics trends as identified using PCA. Dashed lines indicate regions where data interpolation was performed for PCA calculations.
Mentions: Integrating transcriptome and proteome data with available functional information yields valuable biological insights. A careful examination of Figure 5 reveals that several mRNA and proteins are regulated at a pathway or sub-pathway level. It is evident that, in a number of cases, even when dissonant trends are observed between mRNA and protein profiles (discovered using PCA), such behaviors are usually conserved across at least a few functionally related and/or chromosomally linked genes. Figure 6 shows some interesting profiles that fall in this category. Surprisingly certain groups of genes exhibited not just discordant, but contrasting mRNA-protein profiles. These include a putative protein secretion system (SCO1515–1517; Figure 6A), a glutamate uptake system (GluABCD, SCO5774–77; Figure 6B) and a xylose uptake system (SCO6008–6011; Figure 6C). In each case, the proteins exhibited a two- to eight-fold increase in abundance upon entry into stationary phase while the corresponding transcripts displayed a concomitant two- to four-fold down-regulation. Another set of genes is comprised of those for which the protein levels remained relatively constant while mRNA amounts decreased rapidly in stationary phase, hinting at lower rates of protein turnover than mRNA. These include RNA polymerase subunits (RpoBC, SCO4654/55; Figure 6D), phosphoribosyl transferases/ribosomal proteins (SCO3122–24; Figure 6E), a set of ABC transporters (BkdBC, SCO5113/14; Figure 6F), ATP synthase subunits (AtpABC, SCO5367/71/74; Figure 6G), a set of chromosomally linked hypothetical proteins (SCO1651/1655, Figure 6H) and succinate dehydrogenase subunits (DhsAB, SCO4855/56; Figure 6I). Several other distinct profiles were also observed including cases where mRNA was transiently up-regulated but subsequently down-regulated while protein levels remained constant (Figure 6K and 6L) or displayed an increase during transition to stationary phase (Figure 6J). However, the most common type of divergent behavior was differing degrees of differential patterns in largely the same direction. Four such examples are shown in Figure 6 – a set of arginine biosynthesis genes (SCO1222–23; Figure 6M; up-regulated), oxidative stress response genes (AhpCD, SCO5031–32; Figure 6N; down-regulated), fatty acid biosynthesis genes (FabDHF, SCO2387/88/90; Figure 6O; down-regulated) and two other chromosomally linked proteins (DNA-binding protein Hu and malate oxidoreductase, SCO2950/51; Figure 6P).

Bottom Line: Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels.Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends.Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.

Show MeSH
Related in: MedlinePlus