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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

335 Scopus citations

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.

Original language	English
Article number	1259038
Journal	Science
Volume	347
Issue number	6226
DOIs	https://doi.org/10.1126/science.1259038
State	Published - 6 Mar 2015
Externally published	Yes

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Jovanovic, M., Rooney, M. S., Mertins, P., Przybylski, D., Chevrier, N., Satija, R., Rodriguez, E. H., Fields, A. P., Schwartz, S., Raychowdhury, R., Mumbach, M. R., Eisenhaure, T., Rabani, M., Gennert, D., Lu, D., Delorey, T., Weissman, J. S., Carr, S. A., Hacohen, N., & Regev, A. (2015). Dynamic profiling of the protein life cycle in response to pathogens. Science, 347(6226), Article 1259038. https://doi.org/10.1126/science.1259038

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title = "Dynamic profiling of the protein life cycle in response to pathogens",

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.",

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

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doi = "10.1126/science.1259038",

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Jovanovic, M, Rooney, MS, Mertins, P, Przybylski, D, Chevrier, N, Satija, R, Rodriguez, EH, Fields, AP, Schwartz, S, Raychowdhury, R, Mumbach, MR, Eisenhaure, T, Rabani, M, Gennert, D, Lu, D, Delorey, T, Weissman, JS, Carr, SA, Hacohen, N & Regev, A 2015, 'Dynamic profiling of the protein life cycle in response to pathogens', Science, vol. 347, no. 6226, 1259038. https://doi.org/10.1126/science.1259038

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AU - Rooney, Michael S.

AU - Mertins, Philipp

AU - Przybylski, Dariusz

AU - Chevrier, Nicolas

AU - Satija, Rahul

AU - Rodriguez, Edwin H.

AU - Fields, Alexander P.

AU - Schwartz, Schraga

AU - Raychowdhury, Raktima

AU - Mumbach, Maxwell R.

AU - Eisenhaure, Thomas

AU - Rabani, Michal

AU - Gennert, Dave

AU - Lu, Diana

AU - Delorey, Toni

AU - Weissman, Jonathan S.

AU - Carr, Steven A.

AU - Hacohen, Nir

AU - Regev, Aviv

PY - 2015/3/6

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N2 - 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.

AB - 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.

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Dynamic profiling of the protein life cycle in response to pathogens

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