title: Regulation of the Neurospora circadian clock by an RNA helicase.
abstract: The eukaryotic circadian oscillators consist of autoregulatory negative-feedback loops. FRQ, WC-1, and WC-2 are three known components of the negative-feedback loop of the Neurospora circadian oscillator. FRQ represses its own transcription by interacting with the WC-1/WC-2 complex and inhibiting WC's role in transcriptional activation. Here we show that all FRQ associates with FRH, an essential DEAD box-containing RNA helicase in Neurospora. The budding yeast homolog of FRH, Dob1p/Mtr4p, is a cofactor of exosome, an important regulator of RNA metabolism in eukaryotes. Down-regulation of FRH by inducible expression of a hairpin RNA leads to low levels of FRQ but high levels of frq RNA and the abolishment of circadian rhythmicities. FRH is associated with the WC complex and this interaction is maintained in a frq null strain. Disruption of the FRQ-FRH complex by deleting a domain in FRQ eliminates the FRQ-WC interaction, suggesting that FRH mediates the interaction between FRQ and the WC complex. These data demonstrate that FRH is an essential component in the circadian negative-feedback loop and reveal an unexpected role of an RNA helicase in regulating gene transcription.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Qiyang
authors.initials: Q
authors.lastname: He
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics; D009492:Neurospora crassa / Q000235:genetics* / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D014157:Transcription Factors; C105589:wc-1 protein, Neurospora crassa; C103772:white collar 2 protein, Neurospora; D020365:RNA Helicases