RT Journal Article SR Electronic T1 Negative feedback defining a circadian clock: autoregulation of the clock gene frequency JF Science JO Science FD American Association for the Advancement of Science SP 1578 OP 1584 DO 10.1126/science.8128244 VO 263 IS 5153 A1 Aronson, BD A1 Johnson, KA A1 Loros, JJ A1 Dunlap, JC YR 1994 UL http://science.sciencemag.org/content/263/5153/1578.abstract AB 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.