Interconnected feedback loops in the Neurospora circadian system.

In Neurospora crassa, white collar 1 (WC-1), a transcriptional activator and positive clock element, is rhythmically expressed from a nonrhythmic steady-state pool of wc-1 transcript, consistent with posttranscriptional regulation of rhythmicity. Mutations in frq influence both the level and periodicity of WC-1 expression, and driven FRQ expression not only depresses its own endogenous levels, but positively regulates WC-1 synthesis with a lag of about 8 hours, a delay similar to that seen in the wild-type clock. FRQ thus plays dual roles in the Neurospora clock and thereby, with WC-1, forms a second feedback loop that would promote robustness and stability in this circadian system. The existence also of interlocked loops in Drosophila melanogaster and mouse clocks suggests that such interlocked loops may be a conserved aspect of circadian timing systems.