Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and catabolic functions in Neurospora

Sancar, Cigdem; Sancar, Gencer; Ha, Nati; Cesbron, François; Brunner, Michael

doi:10.1186/s12915-015-0126-4

Cited by 70 publications

(98 citation statements)

References 64 publications

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“…As translation is one of the most energy-demanding processes in the cell, it makes sense to coordinate protein translation to times of day when energy levels are highest. In N. crassa, clock-controlled mRNAs generally peak at two phases, dawn and dusk, with dusk phase enriched for genes involved in ATP-requiring anabolic processes and dawn phase enriched for genes involved in ATP-generating catabolism (1,2). Based on our data showing that the levels of P-eEF-2 peak during the day, we predict increased rates of mRNA translation at night, directly following the peak production of ATP during the day, and in coordination with other anabolic processes, including lipid and nucleotide metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Depending on the organism and tissue, nearly half of an organism's expressed genes are under control of the circadian clock at the level of transcription (1)(2)(3)(4). However, mounting evidence indicates a role for the clock in controlling posttranscriptional mechanisms (5), including translation initiation (6,7), whereas clock control of translation elongation has not been investigated.…”

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confidence: 99%

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Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

Caster

Castillo

Sachs

et al. 2016

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

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The circadian clock has a profound effect on gene regulation, controlling rhythmic transcript accumulation for up to half of expressed genes in eukaryotes. Evidence also exists for clock control of mRNA translation, but the extent and mechanisms for this regulation are not known. In Neurospora crassa, the circadian clock generates daily rhythms in the activation of conserved mitogen-activated protein kinase (MAPK) pathways when cells are grown in constant conditions, including rhythmic activation of the well-characterized p38 osmosensing (OS) MAPK pathway. Rhythmic phosphorylation of the MAPK OS-2 (P-OS-2) leads to temporal control of downstream targets of OS-2. We show that osmotic stress in N. crassa induced the phosphorylation of a eukaryotic elongation factor-2 (eEF-2) kinase, radiation sensitivity complementing kinase-2 (RCK-2), and that RCK-2 is necessary for high-level phosphorylation of eEF-2, a key regulator of translation elongation. The levels of phosphorylated RCK-2 and phosphorylated eEF-2 cycle in abundance in wild-type cells but not in cells deleted for OS-2 or the core clock component FREQUENCY (FRQ). Translation extracts from cells grown in constant conditions show decreased translational activity in the late subjective morning, coincident with the peak in eEF-2 phosphorylation, and rhythmic translation of glutathione S-transferase (GST-3) from constitutive mRNA levels in vivo is dependent on circadian regulation of eEF-2 activity. In contrast, rhythms in phosphorylated eEF-2 levels are not necessary for rhythms in accumulation of the clock protein FRQ, indicating that clock control of eEF-2 activity promotes rhythmic translation of specific mRNAs.C ircadian rhythms are the outward manifestation of an endogenous clock mechanism common to nearly all eukaryotes. Depending on the organism and tissue, nearly half of an organism's expressed genes are under control of the circadian clock at the level of transcription (1-4). However, mounting evidence indicates a role for the clock in controlling posttranscriptional mechanisms (5), including translation initiation (6, 7), whereas clock control of translation elongation has not been investigated.The driver of circadian rhythms in Neurospora crassa is an autoregulatory molecular feedback loop composed of the negative elements FREQUENCY (FRQ) and FRQ RNA-interacting helicase (FRH), which inhibit the activity of the positive elements WHITE COLLAR-1 (WC-1) and WC-2 (8-11). WC-1 and WC-2 heterodimerize to form the white collar complex (WCC), which activates transcription of frequency (frq) (8,12,13) and activates transcription of a large set of downstream target genes important for overt rhythmicity (2, 14). One gene directly controlled by the WCC is os-4, which encodes the mitogen-activated protein kinase kinase kinase (MAPKKK) in the osmotically sensitive (OS) MAPK pathway (15). Rhythmic transcription of os-4 leads to rhythmic accumulation of the phosphorylated active form of the downstream p38-like mitogen-activated protein kinase (MAPK) OS-2 (16). In Sac...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

Caster

Castillo

Sachs

et al. 2016

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

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“…Larger scale and more sensitive differential screens identified further ccg s (Bell-Pedersen et al, 1996) but it was not until EST and microarray technology was developed that ccg s in the clock could be tracked at global levels (Correa et al, 2003; Dong et al, 2008; Nowrousian et al, 2003; Zhu et al, 2001), identifying hundreds of potential ccg s of which many were linked to metabolic output. However, recent improvements in technology have allowed for ccg s to be more thoroughly and sensitively tracked using RNA-seq, demonstrating that as much as 40% of the Neurospora genome could be regulated by the circadian clock (Hurley et al, 2014; Sancar et al, 2015). …”

Section: Circadian Outputmentioning

confidence: 99%

“…Genes up-regulated in the circadian afternoon and evening are less involved in metabolic output but are enriched in pathways like protein synthesis. It appears that the distinct dusk and dawn phasing of the clock organizes the molecular output of the cell so that catabolic reactions occur in the morning while anabolic reactions occur at dusk (Dong et al, 2008; Hurley et al, 2014; Sancar et al, 2015). For example, genes involved in ribosome biogenesis and translation peak in the circadian dusk to early evening while genes involved in downstream functions involving proteins, i.e.…”

Section: The Circadian Clock In Neurospora Controls Metabolic Outputmentioning

confidence: 99%

“…CSP-1 is also a Zn-finger transcription factor that can act as a circadian repressor (Sancar et al, 2011). Genes regulated by CSP-1 are repressed in the circadian morning and activated in the circadian evening, suggesting that CSP-1 plays a role in properly timing the expression of circadian output genes (Sancar et al, 2015; Sancar et al, 2011). …”

Section: Metabolic Feedback On the Circadian Clockmentioning

confidence: 99%

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The circadian system as an organizer of metabolism

Hurley

Loros

Dunlap

2016

Fungal Genetics and Biology

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The regulation of metabolism by circadian systems is believed to be a key reason for the extensive representation of circadian rhythms within the tree of life. Despite this, surprisingly little work has focused on the link between metabolism and the clock in Neurospora, a key model system in circadian research. The analysis that has been performed has focused on the unidirectional control from the clock to metabolism and largely ignored the feedback from metabolism on the clock. Recent efforts to understand these links have broken new ground, revealing bidirectional control from the clock to metabolism and vise-versa, showing just how strongly interconnected these two cellular systems can be in fungi. This review describes both well understood and emerging links between the clock and metabolic output of fungi as well as the role that metabolism plays in influencing the rhythm set by the clock.

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Circadian Rhythms inNeurospora

Hurley¹

2020

Encyclopedia of Life Sciences

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Circadian rhythms are highly conserved, 24‐h physiological cycles that, through the ideal programming of behaviour, enhance fitness by ensuring many organismal functions are optimally synchronised with the appropriate phase of the day. Circadian rhythms are controlled via an intracellular, highly regulated, transcription‐translation based negative feedback loop, or ‘clock’, and this feedback loop directly or indirectly impacts a large portion of the genome. Over half a century, genetic and molecular analysis of the circadian system of Neurospora crassa has uncovered a number of paradigms now seen to be universal in the operation of circadian rhythms. This article summarises what is currently understood about the mechanisms that underly circadian regulation in Neurospora and highlights many of the contributions Neurospora has made to understanding these same mechanisms in higher eukaryotes. Neurospora crassa is a key model system for eukaryotic clocks. The Neurospora clock comprises a transcription‐translation negative feedback loop. Intrinsic protein disorder is essential for clock function in Neurospora . The Neurospora clock extensively regulates physiological output. Circadian output is regulated at the transcriptional as well as posttranscriptional levels. The Neurospora clock is resistant to environmental effects while remaining sensitive to environmental cues. Light, temperature and metabolic conditions are all environmental cues that can impact the oscillations of the circadian system.

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Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and catabolic functions in Neurospora

Cited by 70 publications

References 64 publications

Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2

The circadian system as an organizer of metabolism

Circadian Rhythms inNeurospora

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