Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens

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

doi:10.1126/science.1259038

Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens

Science. 2015 Mar 6;347(6226):1259038. doi: 10.1126/science.1259038. Epub 2015 Feb 12.

Authors

Marko Jovanovic¹, Michael S Rooney², Philipp Mertins¹, Dariusz Przybylski¹, Nicolas Chevrier³, Rahul Satija¹, Edwin H Rodriguez⁴, Alexander P Fields⁴, Schraga Schwartz¹, Raktima Raychowdhury¹, Maxwell R Mumbach¹, Thomas Eisenhaure⁵, Michal Rabani¹, Dave Gennert¹, Diana Lu¹, Toni Delorey¹, Jonathan S Weissman⁶, Steven A Carr¹, Nir Hacohen⁷, Aviv Regev⁸

Affiliations

¹ The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
² 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.
³ 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.
⁴ Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94158, USA.
⁵ The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ 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.
⁷ 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.
⁸ 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.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry
Amino Acids / 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
RNA, Messenger / genetics
Sequence Analysis, RNA

Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens

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