How Fungi Keep Time: Circadian Oscillators And Rhythmic Outputs

Deborah Bell-Pedersen (October 26, 2010)

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About 20% of Neurospora genes are under control of the circadian clock system at the level of transcript accumulation, and the bulk of the clock-controlled mRNAs have peak accumulation in the late night to early morning. These data suggested the existence of global mechanisms for rhythmic control of gene expression. Consistent with this idea, we found that the Neurospora OS pathway, a phosphorelay signal transduction pathway that responds to changes in osmotic stress, functions as an output pathway from the FRQ/WCC. ChIP/Solexa sequencing with known oscillator proteins revealed that phosophorelay/MAPK pathway components are direct targets of the White Colar Complex (WCC), providing a direct connection between the clock and the output pathway. Activation of the OS pathway by the FRQ/WCC oscillator culminates in rhythmic OS-2 MAPK activity, which through time-of-day-specific activation of downstream effector molecules, controls rhythms in several target clock-controlled genes. Hijacking conserved signaling pathways by the circadian clock provides a new paradigm for global rhythmic control of target genes of the pathway.