The molecular workings of the Neurospora biological clock.

Jan 10, 2004Novartis Foundation symposium

How the biological clock works at the molecular level in Neurospora

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Circadian Biology on OpenScience ↗PubMed ↗

Abstract

A circadianly regulated gene mutation was identified that disrupts the FRQ-less oscillator (FLO) and affects period length in Neurospora with a functioning clock.

The FRQ/WC feedback loop is essential for the function of the circadian clock in Neurospora crassa.
FRQ levels oscillate with the same period as the circadian cycle and are rapidly induced by light.
The transcriptional activation of frq requires a complex of White Collar proteins (WC-1 and WC-2).
Light-induced transcription of frq is mediated by WCC binding to specific elements in the frq promoter.
The identified mutation affects both FLO and the circadian clock, leading to a shorter period and temperature response defects.

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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.

The molecular workings of the Neurospora biological clock.

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