title: Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered neurospora clock protein FRQ.
abstract: Protein conformation dictates a great deal of protein function. A class of naturally unstructured proteins, termed intrinsically disordered proteins (IDPs), demonstrates that flexibility in structure can be as important mechanistically as rigid structure. At the core of the circadian transcription/translation feedback loop in Neurospora crassa is the protein FREQUENCY (FRQ), shown here shown to share many characteristics of IDPs. FRQ in turn binds to FREQUENCY-Interacting RNA Helicase (FRH), whose clock function has been assumed to relate to its predicted helicase function. However, mutational analyses reveal that the helicase function of FRH is not essential for the clock, and a region of FRH distinct from the helicase region is essential for stabilizing FRQ against rapid degradation via a pathway distinct from its typical ubiquitin-mediated turnover. These data lead to the hypothesis that FRQ is an IDP and that FRH acts nonenzymatically, stabilizing FRQ to enable proper clock circuitry/function.
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Jennifer M
authors: JM
authors: Hurley
authors: Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors: Luis F
authors: LF
authors: Larrondo
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Jennifer J
authors: JJ
authors: Loros
authors: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Electronic address: jay.c.dunlap@dartmouth.edu.
authors: Jay C
authors: JC
authors: Dunlap
mesh_terms: D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D064267:Intrinsically Disordered Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009492:Neurospora crassa / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D010641:Phenotype; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D059748:Proteolysis; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D064267:Intrinsically Disordered Proteins; D011994:Recombinant Proteins; D056926:CLOCK Proteins; D020365:RNA Helicases