The molecular workings of the Neurospora biological clock

Abstract

In Neurosporacrassa the FRQ/WC feedback loop has been shown to be central to the function of the circadian clock. Similar to other eukaryotic systems it is based on a transcription-translation PAS heterodimer type feedback. FRQ levels cycle with a period identical to that of the Neurospora circadian cycle and its expression is rapidly induced by light. A complex of White Collar 1 (WC-1) and White Collar 2 (WC-2) (the WCC) is required for the transcriptional activation of frq. The oscillation in frq message is transcriptionally regulated via a single necessary and sufficient cis-acting element in the frq promoter, the Clock-Box (CB) bound by WCC. Light-induction of frq transcription is mediated by WCC binding to two cis-acting elements (LREs) in the frq promoter. WC-1, with flavin adenine dinucleotide (FAD) as a cofactor, is the blue-light photoreceptor. The original description of a frq-null strain, frq9, (Loros et al 1986) included a description of oscillations in asexual conidial banding that occasionally appeared following 3 to 7 days of arrhythmic development now referred to as FLO for FRQ-less oscillator. Unlike the intact clock, FLO period is sensitive to media composition. We have identified a circadianly regulated gene whose mutation interferes with FLO even under temperature entrainment conditions. This same mutation affects the circadian clock in a frq+ background causing a shorter period length as well as temperature response defects. This gene may be an entry point to study the connection between the biological clock and other basic cellular mechanisms.