Negative feedback defining a circadian clock: autoregulation of the clock gene frequency.
The frequency (frq) locus of Neurospora crassa was originally identified in searches for loci encoding components of the circadian clock. The frq gene is now shown to encode a central component in a molecular feedback loop in which the product of frq negatively regulated its own transcript, which resulted in a daily oscillation in the amount of frq transcript. Rhythmic messenger RNA expression was essential for overt rhythmicity in the organism and no amount of constitutive expression rescued normal rhythmicity in frq loss-of-function mutants. Step reductions in the amount of FRQ-encoding transcript set the clock to a specific and predicted phase. These results establish frq as encoding a central component in a circadian oscillator.
Aronson
B D
BD
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.
Johnson
K A
KA
Loros
J J
JJ
Dunlap
J C
JC
D001483:Base Sequence; D001683:Biological Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D003624:Darkness; D005246:Feedback; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D005787:Gene Frequency; D005800:Genes, Fungal; D006706:Homeostasis; D008027:Light; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics* / Q000502:physiology; D016366:Open Reading Frames; D011801:Quinic Acid / Q000494:pharmacology; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014170:Transformation, Genetic
D005656:Fungal Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D011801:Quinic Acid