NEGATIVE FEEDBACK DEFINING A CIRCADIAN CLOCK - AUTOREGULATION OF THE CLOCK GENE-FREQUENCY

The frequency(frq) locus of Neurospora crassa was originally identifie d in searches for loci encoding components of the circadian clock. The frq gene is now shown to encode a central component in a molecular fe edback loop in which the product of frq negatively regulated its own t ranscript, 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 r escued normal rhythmicity in frq loss-of-function mutants. Step reduct ions in the amount of FRQ-encoding transcript set the clock to a speci fic and predicted phase. These results establish frq as encoding a cen tral component in a circadian oscillator.