Alternative initiation of translation and time-specific phosphorylation yield multiple forms of the essential clock protein FREQUENCY

The frequency (frq) gene encodes central components of the transcription/translation-based negative-feedback loop comprising the core of the Neurospora circadian oscillator; posttranscriptional regulation associated with FRQ is surprisingly complex. Alternative use of translation initiation sites gives rise to two forms of FRQ whose levels peak 4-6 hr following the peak of frq transcript. Each form of FRQ is progressively phosphorylated over the course of the day, thus providing a number of temporally distinct FRQ products. The kinetics of these regulatory processes suggest a view of the clock where relatively rapid events involving translational regulation in the synthesis of FRQ and negative feedback of FRQ on fro transcript levels are followed by slower posttranslational regulation, ultimately driving the turnover of FRQ and reactivation of the frq gene.