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

Cell. 1997 May 2;89(3):469-76. doi: 10.1016/s0092-8674(00)80227-5.


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 frq transcript levels are followed by slower posttranslational regulation, ultimately driving the turnover of FRQ and reactivation of the frq gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Clocks / genetics
  • Circadian Rhythm / genetics
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Isomerism
  • Molecular Weight
  • Mutagenesis, Site-Directed / physiology
  • Neurospora / chemistry
  • Neurospora / physiology
  • Phosphorylation
  • Protein Biosynthesis / physiology*
  • Protein Processing, Post-Translational / physiology
  • Time Factors


  • FRQ protein, Neurospora crassa
  • Fungal Proteins