Publication Date:
2015-03-07
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506746/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506746/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- F32 HD075541/HD/NICHD NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1259038. doi: 10.1126/science.1259038. Epub 2015 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Harvard Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. ; Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA. Howard Hughes Medical Institute (HHMI), University of California, San Francisco, San Francisco, CA 94158, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. Harvard Medical School, Boston, MA 02115, USA. aregev@broad.mit.edu nhacohen@mgh.harvard.edu. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA. HHMI, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA. aregev@broad.mit.edu nhacohen@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745177" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acids/chemistry/metabolism
;
Animals
;
Bone Marrow Cells/*immunology
;
Cell Culture Techniques
;
Dendritic Cells/*immunology
;
Host-Pathogen Interactions/*immunology
;
Isotope Labeling/methods
;
Lipopolysaccharides/immunology
;
Mice
;
Mitochondrial Proteins/metabolism
;
*Molecular Dynamics Simulation
;
*Protein Biosynthesis
;
*Proteolysis
;
RNA, Messenger/biosynthesis/genetics
;
Sequence Analysis, RNA
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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