Salad Days in the Rhythms Trade

Dunlap, Jay C.

doi:10.1534/genetics.104.86496

Cited by 25 publications

(17 citation statements)

References 80 publications

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“…Circadian period or expression mutants have been identified in a variety of organisms, including Neurospora, Drosophila, blowflies, Paramecium, Chlamydomonas, Arabidopsis, Synechococcus, hamsters, mice, and humans (reviewed in refs. [1][2][3]. Among these circadian clock gene mutants, the greatest number in a single system have come from screens in Neurospora, where upwards of a dozen different genes have emerged from unbiased screens for genes informative of the circadian system.…”

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confidence: 99%

period -1 encodes an ATP-dependent RNA helicase that influences nutritional compensation of the Neurospora circadian clock

Emerson

Bartholomai

Ringelberg

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Mutants in the period-1 (prd-1) gene, characterized by a recessive allele, display a reduced growth rate and period lengthening of the developmental cycle controlled by the circadian clock. We refined the genetic location of prd-1 and used whole genome sequencing to find the mutation defining it, confirming the identity of prd-1 by rescuing the mutant circadian phenotype via transformation. PRD-1 is an RNA helicase whose orthologs, DDX5 [DEAD (Asp-Glu-Ala-Asp) Box Helicase 5] and DDX17 in humans and DBP2 (Dead Box Protein 2) in yeast, are implicated in various processes, including transcriptional regulation, elongation, and termination, ribosome biogenesis, and mRNA decay. Although prd-1 mutants display a long period (∼25 h) circadian developmental cycle, they interestingly display a WT period when the core circadian oscillator is tracked using a frq-luciferase transcriptional fusion under conditions of limiting nutritional carbon; the core oscillator in the prd-1 mutant strain runs with a long period under glucose-sufficient conditions. Thus, PRD-1 clearly impacts the circadian oscillator and is not only part of a metabolic oscillator ancillary to the core clock. PRD-1 is an essential protein, and its expression is neither light-regulated nor clock-regulated. However, it is transiently induced by glucose; in the presence of sufficient glucose, PRD-1 is in the nucleus until glucose runs out, which elicits its disappearance from the nucleus. Because circadian period length is carbon concentration-dependent, prd-1 may be formally viewed as a clock mutant with defective nutritional compensation of circadian period length.T he successful dissection of the molecular bases of circadian rhythms by the circadian community over the past three decades has been anchored, in every system from cyanobacteria to mammals, on the products of classical genetic screens for, and analysis of, circadian clock mutants, their molecular cloning, and the conservation of their function. Circadian period or expression mutants have been identified in a variety of organisms, including Neurospora, Drosophila, blowflies, Paramecium, Chlamydomonas, Arabidopsis, Synechococcus, hamsters, mice, and humans (reviewed in refs. 1-3). Among these circadian clock gene mutants, the greatest number in a single system have come from screens in Neurospora, where upwards of a dozen different genes have emerged from unbiased screens for genes informative of the circadian system. The protein products and cellular functions of nearly all of these genes are known, and this knowledge has played a central role in elucidation of the transcription/translation feedback loop model for animal and fungal clocks that guides most research on mammalian clock mechanism (reviewed, e.g., in refs. 4 and 5). Among these Neurospora genes, the product and role of the period-1 (prd-1) gene remains undescribed.The prd-1 gene [originally called frq-5 (frq, frequency) and later prd] was isolated in a UV-mutagenesis screen for period length mutants (6). On race tubes, the canonical mu...

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confidence: 99%

period -1 encodes an ATP-dependent RNA helicase that influences nutritional compensation of the Neurospora circadian clock

Emerson

Bartholomai

Ringelberg

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…A circa 24-hr clock allows organisms to predict day-night changes thus providing them benefits for survival (Ouyang et al 1998;Dodd et al 2005). Our understanding of the circadian clock has advanced dramatically since clock genes period and frq were cloned in Drosophila and Neurospora, respectively (Young and Kay 2001;Dunlap 2008). Since then, research on many model organisms has revealed a conserved aspect of regulation in which negative feedback plays an essential role in maintaining a self-sustained circadian clock (Dunlap 1999;Heintzen and Liu 2007;Mackey 2007).…”

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confidence: 99%

FRQ-Interacting RNA Helicase Mediates Negative and Positive Feedback in the Neurospora Circadian Clock

Shi¹,

Collett²,

Loros

et al. 2010

Genetics

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The Neurospora circadian oscillator comprises FREQUENCY (FRQ) and its transcription activator, the White Collar Complex (WCC). Repression of WCC's transcriptional activity by FRQ via negative feedback is indispensable for clock function. An unbiased genetic screen that targeted mutants with defects in negative feedback regulation yielded a fully viable arrhythmic strain bearing a novel allele of FRQ-interacting RNA helicase ( frh), an essential gene that encodes a putative exosome component protein. In the allele, frh R806H , clock function is completely disturbed, while roles of FRQ-interacting RNA helicase (FRH) essential for viability are left intact. FRH R806H still interacts with FRQ, but interaction between the FRQ-FRH R806H complex (FFC) and WCC is severely affected. Phosphorylation of WC-1 is reduced in the mutant leading to constantly elevated WCC activity, which breaks the negative feedback loop. WCC levels are considerably reduced in the mutant, especially those of WC-1, consistent both with loss of positive feedback (FRQ-dependent WC-1 stabilization) and with a reduced level of the FRQ-mediated WCC phosphorylation that leads to high WCC activity accompanied by rapid transcription-associated turnover. FRH overexpression promotes WC-1 accumulation, confirming that FRH together with FRQ plays a role in WC-1 stabilization. Identification of a viable allele of frh, displaying virtually complete loss of both negative and positive circadian feedback, positions FRH as a core component of the central oscillator that is permissive for rhythmicity but appears not to modulate periodicity. Moreover, the results suggest that there are clock-specific roles for FRH that are distinct from the predicted essential exosome-associated functions for the protein.

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“…Jay Dunlap (2008) emphasized the role of this institution in bringing together investigators interested in circadian biology. A major force at this Station was the Dutch microbiologist C. B. van Niel.…”

Section: Caltechmentioning

confidence: 99%

Weaving a Tapestry from Threads Spun by Geneticists: The Series Perspectives on Genetics, 1987–2008

Dove

2016

Genetics

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The Perspectives column was initiated in 1987 when Jan Drake, Editor-in-Chief of GENETICS, invited Jim Crow and William Dove to serve as coeditors of "Anecdotal, Historical, and Critical Commentaries." As the series evolved over 21 years, under the guidance of Crow and Dove, the input of stories told by geneticists from many countries created a panorama of 20th-century genetics. Three recurrent themes are visible: how geneticists have created the science (as solitary investigators, in pairs, or in cooperative groups); how geneticists work hard, but find ways to have fun; and how public and private institutions have sustained the science of genetics, particularly in the United States. This article ends by considering how the Perspectives series and other communication formats can carry forward the core science of genetics from the 20th into the 21st century.

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Salad Days in the Rhythms Trade

Cited by 25 publications

References 80 publications

period -1 encodes an ATP-dependent RNA helicase that influences nutritional compensation of the Neurospora circadian clock

period -1 encodes an ATP-dependent RNA helicase that influences nutritional compensation of the Neurospora circadian clock

FRQ-Interacting RNA Helicase Mediates Negative and Positive Feedback in the Neurospora Circadian Clock

Weaving a Tapestry from Threads Spun by Geneticists: The Series Perspectives on Genetics, 1987–2008

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