Open AccessDifferential dynamics of the mammalian mRNA and protein expression response to misfolding stress
Author(s) -
Cheng Zhe,
Teo Guoshou,
Krueger Sabrina,
Rock Tara M,
Koh Hiromi WL,
Choi Hyungwon,
Vogel Christine
Publication year - 2016
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20156423
Subject(s) - biology , messenger rna , transcriptome , protein biosynthesis , dithiothreitol , gene expression , microbiology and biotechnology , rna , proteostasis , gene , biochemistry , enzyme
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.