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  • Dynamic profiling of the pr...
    Jovanovic, Marko; Rooney, Michael S.; Mertins, Philipp; Przybylski, Dariusz; Chevrier, Nicolas; Satija, Rahul; Rodriguez, Edwin H.; Fields, Alexander P.; Schwartz, Schraga; Raychowdhury, Raktima; Mumbach, Maxwell R.; Eisenhaure, Thomas; Rabani, Michal; Gennert, Dave; Lu, Diana; Delorey, Toni; Weissman, Jonathan S.; Carr, Steven A.; Hacohen, Nir; Regev, Aviv

    Science (American Association for the Advancement of Science), 03/2015, Volume: 347, Issue: 6226
    Journal Article

    How the immune system readies for battleAlthough gene expression is tightly controlled at both the RNA and protein levels, the quantitative contribution of each step, especially during dynamic responses, remains largely unknown. Indeed, there has been much debate whether changes in RNA level contribute substantially to protein-level regulation. Jovanovic et al. built a genome-scale model of the temporal dynamics of differential protein expression during the stimulation of immunological dendritic cells (see the Perspective by Li and Biggin). Newly stimulated functions involved the up-regulation of specific RNAs and concomitant increases in the levels of the proteins they encode, whereas housekeeping functions were regulated posttranscriptionally at the protein level.Science, this issue 10.1126/science.1259038; see also p. 1066 Protein expression is regulated by the production and degradation of messenger RNAs (mRNAs) and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics so as to build a quantitative genomic model of the differential regulation of gene expression in lipopolysaccharide-stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for more than half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction for newly activated cellular functions and by protein life-cycle changes for remodeling of preexisting functions.