The Resonance and Adaptation of Neurospora crassa Circadian and Conidiation Rhyth ms to Short Light-Dark Cycles

Circadian clocks control the physiological and behavioral rhythms to adapt to the environment with a period of ~24 h. However, the influences and mechanisms of the extreme light/dark cycles on the circadian clock remain unclear. We showed that, in Neurospora crassa, both the growth and the microconidia production contribute to adaptation in LD12:12 (12 h light/12 h dark, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY was entrained to the LD cycles when LD > 3:3 while it free ran when T ≤ LD3:3. The conidial rhythmicity can resonate with a series of different LD conditions. Moreover, we demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions. These findings shed new light on the resonance of Neurospora circadian clock and conidiation rhythms to short LD cycles, which may benefit the understandings of both the basic regulatory aspects of circadian clock and the adaptation of physiological rhythms to the extreme conditions.

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The synchronization and adaptation of Neurospora crassa circadian and conidiation rhythms to short light-dark cycles

10.1101/351189 ◽

2018 ◽

Author(s):

Huan Ma ◽

Luyao Li ◽

Jie Yan ◽

Yin Zhang ◽

Weirui Shi ◽

...

Keyword(s):

Circadian Clock ◽

Neurospora Crassa ◽

Metabolic Pathways ◽

Diurnal Rhythms ◽

Daily Rhythms ◽

The Core ◽

Ubiquitin E3 Ligase ◽

Modeling And Experiments ◽

High Intensity Light ◽

Clock Protein

ABSTRACTCircadian clocks control the physiological and behavioral daily rhythms to adapt to the changing environment with a period of ~24 h. However, the influence and mechanism of extreme light-dark cycles on the circadian clock remain unclear. We show that, in the fungus Neurospora crassa under short LD cycles, both the growth rate and the ratio of microconidia production contributes to adaptation in LD12:12 (light for 12 h and dark for 12 h, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY is entrained to the LD cycles when LD>3:3 while it free runs when T≤ LD3:3. We investigated the changes in circadian/diurnal rhythms under a series of different LD conditions, and the results showed that conidial rhythmicity can be adapted to the short LD cycles. We further demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. A high-intensity light induced the expression of a set of downstream genes involved in various metabolic pathways. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions.

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Unveiling the Impact of the Core Circadian Clock Protein FREQUENCY on Output in Neurospora crassa

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.631.31 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Alexander Eric Mosier ◽

Jennifer Marie Hurley

Keyword(s):

Circadian Clock ◽

Neurospora Crassa ◽

The Core ◽

The Impact ◽

Clock Protein

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Synchronizing the Neurospora crassa circadian clock with the rhythmic environment

Biochemical Society Transactions ◽

10.1042/bst0330949 ◽

2005 ◽

Vol 33 (5) ◽

pp. 949-952 ◽

Cited By ~ 4

Author(s):

N. Price-Lloyd ◽

M. Elvin ◽

C. Heintzen

Keyword(s):

Light Intensity ◽

Circadian Clock ◽

Neurospora Crassa ◽

Model Organism ◽

Circadian Clocks ◽

Current Understanding ◽

Signalling Pathways ◽

Selection Pressures ◽

The Earth ◽

Natural Cycles

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.

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Ubiquitin ligase TRAF 2 attenuates the transcriptional activity of the core clock protein BMAL 1 and affects the maximal Per1 mRNA level of the circadian clock in cells

FEBS Journal ◽

10.1111/febs.14595 ◽

2018 ◽

Vol 285 (16) ◽

pp. 2987-3001 ◽

Cited By ~ 4

Author(s):

Suping Chen ◽

Jing Yang ◽

Lu Yang ◽

Yang Zhang ◽

Liang Zhou ◽

...

Keyword(s):

Circadian Clock ◽

Ubiquitin Ligase ◽

Transcriptional Activity ◽

Mrna Level ◽

The Core ◽

Clock Protein ◽

In Cells

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Intrinsic disorder is an essential characteristic of components in the conserved circadian circuit

Cell Communication and Signaling ◽

10.1186/s12964-020-00658-y ◽

2020 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Jacqueline F. Pelham ◽

Jay C. Dunlap ◽

Jennifer M. Hurley

Keyword(s):

Circadian Clock ◽

Neurospora Crassa ◽

Mus Musculus ◽

Intrinsically Disordered Proteins ◽

Intrinsic Disorder ◽

Cellular Systems ◽

Disordered Proteins ◽

Circadian Timing ◽

Intrinsically Disordered ◽

The Core

Abstract Introduction The circadian circuit, a roughly 24 h molecular feedback loop, or clock, is conserved from bacteria to animals and allows for enhanced organismal survival by facilitating the anticipation of the day/night cycle. With circadian regulation reportedly impacting as high as 80% of protein coding genes in higher eukaryotes, the protein-based circadian clock broadly regulates physiology and behavior. Due to the extensive interconnection between the clock and other cellular systems, chronic disruption of these molecular rhythms leads to a decrease in organismal fitness as well as an increase of disease rates in humans. Importantly, recent research has demonstrated that proteins comprising the circadian clock network display a significant amount of intrinsic disorder. Main body In this work, we focus on the extent of intrinsic disorder in the circadian clock and its potential mechanistic role in circadian timing. We highlight the conservation of disorder by quantifying the extent of computationally-predicted protein disorder in the core clock of the key eukaryotic circadian model organisms Drosophila melanogaster, Neurospora crassa, and Mus musculus. We further examine previously published work, as well as feature novel experimental evidence, demonstrating that the core negative arm circadian period drivers FREQUENCY (Neurospora crassa) and PERIOD-2 (PER2) (Mus musculus), possess biochemical characteristics of intrinsically disordered proteins. Finally, we discuss the potential contributions of the inherent biophysical principals of intrinsically disordered proteins that may explain the vital mechanistic roles they play in the clock to drive their broad evolutionary conservation in circadian timekeeping. Conclusion The pervasive conservation of disorder amongst the clock in the crown eukaryotes suggests that disorder is essential for optimal circadian timing from fungi to animals, providing vital homeostatic cellular maintenance and coordinating organismal physiology across phylogenetic kingdoms. Graphical abstract

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Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms

10.1101/2020.10.09.333732 ◽

2020 ◽

Author(s):

Yangbo Xiao ◽

Ye Yuan ◽

Mariana Jimenez ◽

Neeraj Soni ◽

Swathi Yadlapalli

Keyword(s):

Gene Expression ◽

Circadian Rhythms ◽

Nuclear Envelope ◽

Circadian Clock ◽

Clock Genes ◽

Circadian Clocks ◽

Spatiotemporal Organization ◽

Clock Proteins ◽

Expression Behavior ◽

Clock Protein

ABSTRACTCircadian clocks regulate ∼24 hour oscillations in gene expression, behavior, and physiology. While the molecular and neural mechanisms of circadian rhythms are well characterized, how cellular organization of clock components controls circadian clock regulation remains poorly understood. Here, we elucidate how clock proteins regulate circadian rhythms by controlling the spatiotemporal organization of clock genes. Using high-resolution live imaging techniques we demonstrate that Drosophila clock proteins are concentrated in a few discrete foci and are organized at the nuclear envelope; these results are in contrast to longstanding expectations that clock proteins are diffusely distributed in the nucleus. We also show that clock protein foci are highly dynamic and change in number, size, and localization over the circadian cycle. Further, we demonstrate that clock genes are positioned at the nuclear periphery by the clock proteins precisely during the circadian repression phase, suggesting that subnuclear localization of clock genes plays an important role in the control of rhythmic gene expression. Finally, we show that Lamin B receptor, a nuclear envelope protein, is required for peripheral localization of clock protein foci and clock genes and for normal circadian rhythms. These results reveal that clock proteins form dynamic nuclear foci and play a hitherto unexpected role in the subnuclear reorganization of clock genes to control circadian rhythms, identifying a novel mechanism of circadian regulation. Our results further suggest a new role for clock protein foci in the clustering of clock-regulated genes during the repression phase to control gene co-regulation and circadian rhythms.SIGNIFICANCEAlmost all living organisms have evolved circadian clocks to tell time. Circadian clocks regulate ∼24-hour oscillations in gene expression, behavior and physiology. Here, we reveal the surprisingly sophisticated spatiotemporal organization of clock proteins and clock genes and its critical role in circadian clock function. We show, in contrast to current expectations, that clock proteins are concentrated in a few discrete, dynamic nuclear foci at the nuclear envelope during the repression phase. Further, we uncovered several unexpected features of clock protein foci, including their role in positioning the clock genes at the nuclear envelope precisely during the repression phase to enable circadian rhythms. These studies provide fundamental new insights into the cellular mechanisms of circadian rhythms and establish direct links between nuclear organization and circadian clocks.

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Identification and regulation of a circadian clock protein, FRQ, and a clock-controlled protein, CCG-1, in Neurospora crassa.

10.1349/ddlp.1502 ◽

1996 ◽

Cited By ~ 1

Author(s):

Norman Y. Garceau

Keyword(s):

Circadian Clock ◽

Neurospora Crassa ◽

Clock Protein

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The sweet tooth of the circadian clock

Biochemical Society Transactions ◽

10.1042/bst20160183 ◽

2017 ◽

Vol 45 (4) ◽

pp. 871-884 ◽

Cited By ~ 3

Author(s):

Minnie Fu ◽

Xiaoyong Yang

Keyword(s):

Circadian Clock ◽

Metabolic Response ◽

Circadian Clocks ◽

Molecular Clocks ◽

Post Translational Modifications ◽

The Core ◽

Input And Output ◽

Intracellular Proteins ◽

Translational Mechanisms

The endogenous circadian clock is a key regulator of daily metabolic processes. On the other hand, circadian clocks in a broad range of tissues can be tuned by extrinsic and intrinsic metabolic cues. The bidirectional interaction between circadian clocks and metabolism involves both transcriptional and post-translational mechanisms. Nuclear receptors exemplify the transcriptional programs that couple molecular clocks to metabolism. The post-translational modifications of the core clock machinery are known to play a key role in metabolic entrainment of circadian clocks. O-linked N-acetylglucosamine modification (O-GlcNAcylation) of intracellular proteins is a key mediator of metabolic response to nutrient availability. This review highlights our current understanding of the role of protein O-GlcNAcylation in mediating metabolic input and output of the circadian clock.

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Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery

Nucleic Acids Research ◽

10.1093/nar/gkaa601 ◽

2020 ◽

Vol 48 (14) ◽

pp. 7944-7957

Author(s):

Renbin Lu ◽

Yufan Dong ◽

Jia-Da Li

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Ubiquitin Proteasome System ◽

Circadian Clocks ◽

Clock Gene Expression ◽

Ubiquitin Proteasome ◽

Hsp90 Chaperone ◽

Abnormal Behaviors ◽

Clock Protein

Abstract Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin–proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.

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