title: Synthesis and degradation jointly determine the responsiveness of the cellular proteome.
abstract: It is of fundamental importance to understand how the individual processes of gene expression, transcription, and translation, as well as mRNA and protein stability, act in concert to produce dynamic cellular proteomes. We use the concept of response times to illustrate the relation between degradation processes and responsiveness of the proteome to system changes and to provide supporting experimental evidence: proteins with short response times tend to be more strongly up-regulated after 1 hour of TNFα stimulation than proteins with longer response times. Furthermore, based on process-dependent response times, we demonstrate that synthesis and degradation act in concert to enable rapid responses. Finally, by building on a previously published data set quantifying the mammalian gene expression cascade, we speculate on how combinations of stable and unstable mRNAs and proteins may be wired to transcriptional or translational regulation to support gene function.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schwanhäusser
authors.forename: Jana
authors.initials: J
authors.lastname: Wolf
authors.forename: Matthias
authors.initials: M
authors.lastname: Selbach
authors.forename: Dorothea
authors.initials: D
authors.lastname: Busse
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis / Q000235:genetics*; D020543:Proteome / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D020543:Proteome; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha