PT - JOURNAL ARTICLE AU - Aronson, BD AU - Johnson, KA AU - Loros, JJ AU - Dunlap, JC TI - Negative feedback defining a circadian clock: autoregulation of the clock gene frequency AID - 10.1126/science.8128244 DP - 1994 Mar 18 TA - Science PG - 1578--1584 VI - 263 IP - 5153 4099 - http://science.sciencemag.org/content/263/5153/1578.short 4100 - http://science.sciencemag.org/content/263/5153/1578.full SO - Science1994 Mar 18; 263 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.