Entrainment Dissociates Transcription and Translation of a Circadian Clock Gene in Neurospora

Circadian systems coordinate the daily sequence of events in cells, tissues, and organisms. In constant conditions, the biological clock oscillates with its endogenous period, whereas it is synchronized to the 24 hr light:dark cycle in nature. Here, we investigate light entrainment of Neurospora crassa to photoperiods that mimic seasonal changes. Clock gene (frequency, or frq) RNA levels directly reflect the light environment in all photoperiods, whereas the FRQ protein follows neither RNA levels nor light transitions. Induction of frq RNA and protein can be dissociated by as much as 6 hr, depending on photoperiod. The phase of entrainment at the physiological level (e.g., asexual spore development) correlates with FRQ protein. Thus, a dissociation of transcription, translation, and protein stability is fundamental to circadian entrainment of Neurospora. Our findings suggest that simple feedback models are insufficient to explain the molecular circadian mechanisms under entrained conditions and that clock control of light input pathways involves posttranscriptional regulation. The regulators mediating the dissociation between RNA and protein levels are still unknown and will be the key to understanding both circadian timing at the molecular level and how the clock exerts control over many cellular processes.