Structure of the frequency‐interacting RNA helicase: a protein interaction hub for the circadian clock. (23rd June 2016) - Conrad, Karen S
Abstract: In the Neurospora crassa circadian clock, a protein complex of frequency (FRQ), casein kinase 1a (CK1a), and the FRQ‐interacting RNA Helicase (FRH) rhythmically represses gene expression by the white‐collar complex (WCC). FRH crystal structures in several conformations and bound to ADP/RNA reveal differences between FRH and the yeast homolog Mtr4 that clarify the distinct role of FRH in the clock. The FRQ‐interacting region at the FRH N‐terminus has variable structure in the absence of FRQ. A known mutation that disrupts circadian rhythms (R806H) resides in a positively charged surface of the KOW domain, far removed from the helicase core. We show that changes to other similarly located residues modulate interactions with the WCC and FRQ. A V142G substitution near the N‐terminus also alters FRQ and WCC binding to FRH, but produces an unusual short clock period. These data support the assertion that FRH helicase activity does not play an essential role in the clock, but rather FRH acts to mediate contacts among FRQ, CK1a and the WCC through interactions involving its N‐terminus and KOW module. Synopsis: The structure of the frequency‐interacting RNA helicase (FRH) reveals elements that allow FRH to coordinate interactions among key components of the central transcriptional–translational feedback loop in the fungal circadian clock. FRH resembles housekeeping RNA helicases, but helicase activity is not essential for its clock function. An N‐terminal region unique to FRH that binds to the primary clock repressor frequency (FRQ) has highly variable structure in the absence of FRQ. The FRH KOW domain exists in different conformations and mediates contacts between FRH, FRQ, and the members of the White‐Collar transcription complex. Single residue changes in the FRH N‐terminus and KOW domain affect interactions with other clock components and can perturb circadian rhythms. Abstract : The structure of the frequency‐interacting RNA helicase (FRH) reveals elements that allow FRH to coordinate interactions among key components of the central transcriptional–translational feedback loop in the fungal circadian clock.