Thermally Regulated Translational Control of FRQ Mediates Aspects of Temperature Responses in the Neurospora Circadian Clock

Two forms of FRQ, a central component of the Neurospora circadian clock, arise through alternative in-frame initiation of translation. Either form alone suffices for a functional clock at some temperatures, but both are always necessary for robust rhythmicity. Temperature regulates the ratio of FRQ forms by favoring different initiation codons at different temperatures; when either initiation codon is eliminated, the temperature range permissive for rhythmicity is demon- strably reduced. This temperature-influenced choice of translation-initiation site represents a novel adaptive mechanism that extends the physiological temperature range over which clocks function. Additionally, a temperature-dependent threshold level of FRQ is required to establish the feedback loop comprising the oscillator. These data may explain how temperature limits permissive for rhythmicity are established, thus providing a molecular understanding for a basic characteristic of circadian clocks.