title: Modulation of Circadian Gene Expression and Metabolic Compensation by the RCO-1 Corepressor of Neurospora crassa.
abstract: Neurospora crassa is a model organism for the study of circadian clocks, molecular machineries that confer ∼24-hr rhythms to different processes at the cellular and organismal levels. The FREQUENCY (FRQ) protein is a central component of the Neurospora core clock, a transcription/translation negative feedback loop that controls genome-wide rhythmic gene expression. A genetic screen aimed at determining new components involved in the latter process identified regulation of conidiation 1 (rco-1), the ortholog of the Saccharomyces cerevisiae Tup1 corepressor, as affecting period length. By employing bioluminescent transcriptional and translational fusion reporters, we evaluated frq and FRQ expression levels in the rco-1 mutant background observing that, in contrast to prior reports, frq and FRQ expression are robustly rhythmic in the absence of RCO-1, although both amplitude and period length of the core clock are affected. Moreover, we detected a defect in metabolic compensation, such that high-glucose concentrations in the medium result in a significant decrease in period when RCO-1 is absent. Proteins physically interacting with RCO-1 were identified through co-immunoprecipitation and mass spectrometry; these include several components involved in chromatin remodeling and transcription, some of which, when absent, lead to a slight change in period. In the aggregate, these results indicate a dual role for RCO-1: although it is not essential for core-clock function, it regulates proper period and amplitude of core-clock dynamics and is also required for the rhythmic regulation of several clock-controlled genes.
authors.affiliation: Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago RM 114-D, Chile.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Olivares-Yañez
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Jillian
authors.initials: J
authors.lastname: Emerson
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Arminja
authors.initials: A
authors.lastname: Kettenbach
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755 Department of Biochemistry, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Loros
authors.affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Dunlap
authors.affiliation: Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago RM 114-D, Chile llarrondo@bio.puc.cl.
authors.forename: Luis F
authors.identifier: 0000-0002-8832-7109
authors.initials: LF
authors.lastname: Larrondo
mesh_terms: D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics*; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D009492:Neurospora crassa / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; C102112:RCO-1 protein, Neurospora crassa; D012097:Repressor Proteins
keywords: Neurospora crassa; circadian clocks; core-clock mechanism; corepressor; frequency