A developmental cycle masks output from the circadian oscillator under conditions of choline deficiency in
            <i>Neurospora</i>

Shi, Mi; Larrondo, Luis F.; Loros, Jennifer J.; Dunlap, Jay C.

doi:10.1073/pnas.0706631104

Cited by 24 publications

(22 citation statements)

References 55 publications

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“…These FLOs are metabolic oscillators that lack circadian characteristics but that can under some conditions wrest control of development from the circadian system so that the overt appearance of conidiation on race tubes presents as a non-temperature-compensated growth medium-dependent rhythm (27). For instance, prd-1 has been shown to influence membrane fatty acid composition and alter the effects of exogenous fatty acid supplements on certain FLOs (28,29) and to abolish another FLO that can appear upon starvation for choline (30).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The ability to follow both chol-1 and frq rhythms has exposed independent oscillators in a common cytoplasm. (Reprinted, with permission, from Shi et al 2007 [© National Academy of Sciences].) ATM/ATR following DNA damage, and once activated, it phosphorylates a number of target genes, one of which is FRQ.…”

Section: Discussionmentioning

confidence: 99%

Circadian Output, Input, and Intracellular Oscillators: Insights into the Circadian Systems of Single Cells

Loros¹,

Dunlap²,

Larrondo³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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Circadian output comprises the business end of circadian systems in terms of adaptive significance. Work on Neurospora pioneered the molecular analysis of circadian output mechanisms, and insights from this model system continue to illuminate the pathways through which clocks control metabolism and overt rhythms. In Neurospora, virtually every strain examined in the context of rhythms bears the band allele that helps to clarify the overt rhythm in asexual development. Recent cloning of band showed it to be an allele of ras-1 and to affect a wide variety of signaling pathways yielding enhanced light responses and asexual development. These can be largely phenocopied by treatments that increase levels of intracellular reactive oxygen species. Although output is often unidirectional, analysis of the prd-4 gene provided an alternative paradigm in which output feeds back to affect input. prd-4 is an allele of checkpoint kinase-2 that bypasses the requirement for DNA damage to activate this kinase; FRQ is normally a substrate of activated Chk2, so in Chk2 , FRQ is precociously phosphorylated and the clock cycles more quickly. Finally, recent adaptation of luciferase to fully function in Neurospora now allows the core FRQ/WCC feedback loop to be followed in real time under conditions where it no longer controls the overt rhythm in development. This ability can be used to describe the hierarchical relationships among FRQ-Less Oscillators (FLOs) and to see which are connected to the circadian system. The nitrate reductase oscillator appears to be connected, but the oscillator controlling the longperiod rhythm elicited upon choline starvation appears completely disconnected from the circadian system; it can be seen to run with a very long noncompensated 60-120-hour period length under conditions where the circadian FRQ/WCC oscillator continues to cycle with a fully compensated circadian 22-hour period.

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“…None of the double mutant cel or chol-1 strains are damped by constant light or entrain to light/dark cycles (Lakin-Thomas and Brody, 2000). Recent studies examining frq- driven luciferase rhythms in the chol-1 mutant strain revealed that under conditions in which the strain shows a long-period developmental rhythm, the frq :luc rhythms cycled with a 22-h period (Shi et al ., 2007). Although it has been suggested that these data indicate independent functioning of two oscillators (Shi et al ., 2007), the possibility of coupling between two oscillators in a frequency demultiplication relationship has not been fully explored.…”

Section: Frq-less Rhythmsmentioning

confidence: 99%

“…There are several possible interpretations of the data. One view (Shi et al ., 2007) describes FLOs as “metabolic oscillators” and proposes that there are different FLOs driving the observed rhythms for every reported condition; these multiple metabolic oscillators (of which there would need to be more than a dozen at the latest count) are not considered to be connected to the circadian system (Shi et al ., 2007). Another view proposes multiple FLOs that, under normal circumstances, interact with one another and with the FRQ/WCC to produce a network of coupled oscillators, but that individual FLOs may act independently to drive a particular output (de Paula et al ., 2007).…”

Section: Frq-less Rhythmsmentioning

confidence: 99%

The Genetics of Circadian Rhythms in Neurospora

Lakin-Thomas¹,

Bell-Pedersen²,

Brody³

2011

The Genetics of Circadian Rhythms

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This chapter describes our current understanding of the genetics of the Neurospora clock and summarizes the important findings in this area in the past decade. Neurospora is the most intensively studied clock system, and the reasons for this are listed. A discussion of the genetic interactions between clock mutants is included, highlighting the utility of dissecting complex mechanisms by genetic means. The molecular details of the Neurospora circadian clock mechanism are described, as well as the mutations that affect the key clock proteins, FRQ, WC-1, and WC-2, with an emphasis on the roles of protein phosphorylation. Studies on additional genes affecting clock properties are described and place these genes into two categories: those that affect the FRQ/WCC oscillator and those that do not. A discussion of temperature compensation and the mutants affecting this property is included. A section is devoted to the observations pertinent to the existence of other oscillators in this organism with respect to their properties, their effects, and their preliminary characterization. The output of the clock and the control of clock-controlled genes are discussed, emphasizing the phasing of these genes and the layers of control. In conclusion, the authors provide an outlook summarizing their suggestions for areas that would be fruitful for further exploration.

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A developmental cycle masks output from the circadian oscillator under conditions of choline deficiency in Neurospora

Cited by 24 publications

References 55 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

Circadian Output, Input, and Intracellular Oscillators: Insights into the Circadian Systems of Single Cells

The Genetics of Circadian Rhythms in Neurospora

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