title: A genetic network for the clock of Neurospora crassa.
abstract: A diverse array of organisms from bacteria to humans may have evolved the ability to tell time in the presence or absence of external environmental cues. In the lowly bread mould, Neurospora crassa, biomolecular reactions involving the white-collar-1 (wc-1), white-collar-2 (wc-2), and frequency (frq) genes and their products constitute building blocks of a biological clock. Here we use genetic network models to explain quantitatively, from a systems perspective, how these building blocks interact, and how a complex trait like clock oscillation emerges from these interactions. We use a recently developed method of genetic network identification to find an ensemble of oscillating network models quantitatively consistent with available RNA and protein profiling data on the N. crassa clock. Predicted key features of the N. crassa clock system are a dynamically frustrated closed feedback loop, cooperativity in frq gene activation, and/or WC-1/WC-2 protein complex deactivation and substantial posttranscriptional enhancement of wc-1 RNA lifetime. Measuring the wc-1 mRNA lifetime provides a critical test of the genetic networks.
authors.affiliation: Department of Physics and Astronomy, University of Georgia, Athens, GA 30602, USA.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Yu
authors.forename: Wubei
authors.initials: W
authors.lastname: Dong
authors.forename: Cara
authors.initials: C
authors.lastname: Altimus
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Tang
authors.forename: James
authors.initials: J
authors.lastname: Griffith
authors.forename: Melissa
authors.initials: M
authors.lastname: Morello
authors.forename: Lisa
authors.initials: L
authors.lastname: Dudek
authors.forename: Jonathan
authors.initials: J
authors.lastname: Arnold
authors.forename: Heinz-Bernd
authors.initials: HB
authors.lastname: Schüttler
mesh_terms: D001683:Biological Clocks / Q000235:genetics* / Q000528:radiation effects; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000528:radiation effects; D008027:Light; D008957:Models, Genetic; D009492:Neurospora crassa / Q000235:genetics* / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D005656:Fungal Proteins; D012333:RNA, Messenger