Uncovering genes with divergent mRNA-protein dynamics in Streptomyces coelicolor

Karthik P. Jayapal, Robin J. Philp, Yee Jiun Kok, Miranda G S Yap, David H. Sherman, Timothy J. Griffin, Wei Shou Hu

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Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and phsyiological 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 implicity 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.

Original languageEnglish (US)
Article numbere2097
JournalPloS one
Issue number5
StatePublished - May 7 2008

Bibliographical note

Funding Information:
We are grateful to Dr. LeeAnn Higgins and Dr. Lorraine B. Anderson of the Center for Mass Spectrometry and Proteomics (University of Minnesota, USA) and Ms. Zheng Lu of the Bioprocessing Technology Institute (A*STAR, Singapore) for their technical assistance with mass spectrometry. Bioinformatics support was provided by the University of Minnesota Supercomputing Institute.


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