RNA helicase controls both negative and positive feedback in the Neurospora biological clock

A novel allele of the FRQ-interacting RNA helicase gene, frh(R806H), leads to complete disruption of circadian clock function.

• The frh(R806H) allele results in an arrhythmic strain while maintaining essential viability functions of FRH.
• FRH(R806H) interacts with FRQ, but the interaction with the White Collar Complex (WCC) is significantly impaired.
• Reduced phosphorylation of WC-1 in the mutant leads to persistently elevated WCC activity, disrupting the negative feedback loop.
• WCC levels, particularly those of WC-1, are considerably decreased, indicating a loss of positive feedback and reduced FRQ-mediated WCC stabilization.
• Overexpression of FRH increases WC-1 levels, highlighting FRH's role in stabilizing WC-1 alongside FRQ.
• The findings suggest that FRH has clock-specific functions that differ from its expected role in exosome-related processes.

Simplified