Journal
FASEB JOURNAL
Volume 25, Issue 2, Pages 515-525Publisher
WILEY
DOI: 10.1096/fj.10-157529
Keywords
gene expression; development; microarray; proteomics
Categories
Funding
- U.S.-Israel Binational Foundation [2003237]
- Israel Ministry of Health Chief Scientist Foundation [33928]
- Direct For Computer & Info Scie & Enginr [2003237] Funding Source: National Science Foundation
- Division Of Computer and Network Systems [2003237] Funding Source: National Science Foundation
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For many years, mRNA abundance has been used as the surrogate measure of gene expression in biological systems. However, recent genome-scale analyses in both bacteria and eukaryotes have revealed that mRNA levels correlate with steady-state protein abundance for only 50-70% of genes, indicating that translation and post-translation processes also play important roles in determining gene expression. What is not yet clear is whether dynamic processes such as cell cycle progression, differentiation, or response to environmental changes change the relationship between mRNA and protein abundance. Here, we describe a systems approach to interrogate promastigote-to-amastigote differentiation in the obligatory intracellular parasitic protozoan Leishmania donovani. Our results indicate that regulation of mRNA levels plays a major role early in the differentiation process, while translation and post-translational regulation are more important in the latter part. In addition, it appears that the differentiation signal causes a transient global increase in the rate of protein synthesis, which is subsequently down-regulated by phosphorylation of alpha-subunit of translation initiation factor 2. Thus, Leishmania dynamically changes the relationship between mRNA and protein abundance as it adapts to new environmental circumstances. It is likely that similar mechanisms play a more important role than previously recognized in regulation of gene expression in other organisms.-Lahav, T., Sivam, D., Volpin, H., Ronen, M., Tsigankov, P., Green, A., Holland, N., Kuzyk, M., Borchers, C., Zilberstein, D., Myler, P. J. Multiple levels of gene regulation mediate differentiation of the intracellular pathogen Leishmania. FASEB J. 25, 515-525 (2011). www.fasebj.org
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