title: Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress.
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.
authors.affiliation: Center for Genomics and Systems Biology, New York University, New York, NY, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Saw Swee Hock School of Public Health, National University Singapore, Singapore National University Health System, Singapore.
authors.forename: Guoshou
authors.initials: G
authors.lastname: Teo
authors.affiliation: Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Krueger
authors.affiliation: Center for Genomics and Systems Biology, New York University, New York, NY, USA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Rock
authors.affiliation: Saw Swee Hock School of Public Health, National University Singapore, Singapore National University Health System, Singapore.
authors.forename: Hiromi W L
authors.initials: HW
authors.lastname: Koh
authors.affiliation: Saw Swee Hock School of Public Health, National University Singapore, Singapore National University Health System, Singapore hyung_won_choi@nuhs.edu.sg cvogel@nyu.edu.
authors.forename: Hyungwon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Center for Genomics and Systems Biology, New York University, New York, NY, USA hyung_won_choi@nuhs.edu.sg cvogel@nyu.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Vogel
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics*; D007700:Kinetics; D008322:Mammals; D014176:Protein Biosynthesis / Q000235:genetics*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger
keywords: Central Dogma; ER stress; PECA; mammalian proteomics; mass spectrometry