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Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress

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Official URL:https://doi.org/10.15252/msb.20156423
PubMed:View item in PubMed
Creators Name:Cheng, Z. and Teo, G. and Krueger, S. and Rock, T.M. and Koh, H.W.L. and Choi, H. and Vogel, C.
Journal Title:Molecular Systems Biology
Journal Abbreviation:Mol Syst Biol
Volume:12
Number:1
Page Range:855
Date:20 January 2016
Keywords:Central Dogma, ER Stress, Mammalian Proteomics, Mass Spectrometry, PECA, Animals
Abstract:The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse-like pattern and returned to values close to pre-treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes.
ISSN:1744-4292
Publisher:EMBO Press
Additional Information:http://biorxiv.org/content/early/2015/11/26/032797
Item Type:Article

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