title: Small RNAs establish delays and temporal thresholds in gene expression.
abstract: Noncoding RNAs are crucial regulators of gene expression in prokaryotes and eukaryotes, but how they affect the dynamics of transcriptional networks remains poorly understood. We analyzed the temporal characteristics of the cyanobacterial iron stress response by mathematical modeling and quantitative experimental analyses and focused on the role of a recently discovered small noncoding RNA, IsrR. We found that IsrR is responsible for a pronounced delay in the accumulation of isiA mRNA encoding the late-phase stress protein, IsiA, and that it ensures a rapid decline in isiA levels once external stress triggers are removed. These kinetic properties allow the system to selectively respond to sustained (as opposed to transient) stimuli and thus establish a temporal threshold, which prevents energetically costly IsiA accumulation under short-term stress conditions. Biological information is frequently encoded in the quantitative aspects of intracellular signals (e.g., amplitude and duration). Our simulations reveal that competitive inhibition and regulated degradation allow intracellular regulatory networks to efficiently discriminate between transient and sustained inputs.
authors.affiliation: Humboldt University Berlin, Institute for Theoretical Biology, Germany. s.legewie@biologie.hu-berlin.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Legewie
authors.forename: Dennis
authors.initials: D
authors.lastname: Dienst
authors.forename: Annegret
authors.initials: A
authors.lastname: Wilde
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Herzel
authors.forename: Ilka M
authors.initials: IM
authors.lastname: Axmann
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007501:Iron / Q000494:pharmacology; D000090463:Iron Deficiencies; D007700:Kinetics; D045342:Light-Harvesting Protein Complexes / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D018384:Oxidative Stress / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D045342:Light-Harvesting Protein Complexes; D022661:RNA, Untranslated; C076726:chlorophyll A binding protein CP43, Cyanobacteria; D007501:Iron