Negative Feedback Defining a Circadian Clock: Autoregulation of the Clock Gene <i>frequency</i>

TLDR

The frq locus in Neurospora crassa was first identified as a candidate circadian clock component. The frq gene encodes a core component of a negative feedback loop that drives daily oscillations of its own transcript, and rhythmic frq expression is essential for normal circadian rhythms, with graded transcript levels setting clock phase.

Abstract

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.