Interconnected Feedback Loops in the
            <i>Neurospora</i>
            Circadian System

Lee, Kwangwon; Loros, Jennifer J.; Dunlap, Jay C.

doi:10.1126/science.289.5476.107

Cited by 327 publications

(380 citation statements)

References 28 publications

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“…109) showing similarity to a calcium/calmodulin-dependent protein kinase (CAMK-1) also occurred among the sequences down-regulated in the DFvMAT1-2-1 mutant as there is a multiple interaction between the WCC complex and CAMK-1. WCC activates the transcription of frq, a gene encoding the circadian clock protein, FREQUENCY (FRQ), and FRQ -meanwhile repressing frq transcription -exerts a positive feedback on levels of the WC proteins (Lee et al 2000). Posttranslational mechanisms also regulate the circadian clock functions through phosphorylation of these proteins maintaining thus the proper operation of the clock.…”

Section: Discussionmentioning

confidence: 99%

Tagging target genes of the MAT1-2-1 transcription factor in Fusarium verticillioides (Gibberella fujikuroi MP-A)

Keszthelyi

Jeney

Kerényi

et al. 2006

Antonie van Leeuwenhoek

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Mating type in filamentous ascomycetes is controlled by idiomorphic alleles, named MAT1-1 and MAT1-2, which contain 1-3 genes. Of these genes MAT1-1-1 and MAT1-2-1 encode putative transcription factors and are thus considered to be the major regulators of sexual communication and mating. Fungi with no known sexual stage may also have fully functional mating type genes and therefore it was plausible to hypothesize that the MAT products may also regulate other types of genes not involved directly in the mating process. To identify putative target genes of these transcription factors in Fusarium verticillioides, DMAT1-2-1 knock out mutants were produced and transcript profiles of mutant and wild type were compared by means of differential cDNA hybridization. Clones, either up-or down-regulated in the DMAT1-2-1 mutant were sequenced and a total of 248 sequences were blasted against the NCBI database as well as the Gibberella zeae and Gibberella moniliformis genomes. Fifty-five percent of the clones were down-regulated in the mutant, indicating that the MAT1-2-1 product positively affected these tagged sequences. On the other hand, 45% were found to be up-regulated in the mutant, suggesting that the MAT1-2-1 product also exerted a negative regulatory function on this set of genes. Sequences involved in protein synthesis and metabolism occurred more frequently among the clones up-regulated in the mutant, whereas genes belonging to cell signalling and communication were especially frequently tagged among the sequences down-regulated in the mutant.

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Section: Discussionmentioning

confidence: 99%

Tagging target genes of the MAT1-2-1 transcription factor in Fusarium verticillioides (Gibberella fujikuroi MP-A)

Keszthelyi

Jeney

Kerényi

et al. 2006

Antonie van Leeuwenhoek

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“…It involves interlocked feedback loops (Glossop et al 1999;Lee et al 2000;Ripperger & Schibler 2001). Moreover, experiments showed that multiple phosphorylations of the PER protein have differential effects on the protein degradation and translocation in the nucleus (Vanselow et al 2006;Xu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

Gérard

Gonze

Goldbeter

2009

Phil. Trans. R. Soc. A.

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Circadian rhythms, which occur spontaneously with a period of about 24 h in a variety of organisms, allow their adaptation to the periodic variations of the environment. These rhythms are generated by a genetic regulatory network involving a negative feedback loop on transcription. Mathematical models based on the negative autoregulation of gene expression by the protein product of a clock gene account for the occurrence of selfsustained circadian oscillations. These models differ by their degree of complexity and, hence, by the number of variables considered. Some of these models can be considered as minimal because they contain a reduced number of biochemical processes and variables capable of producing sustained oscillations. In three of these minimal models, the period of the oscillations significantly changes with the rate of degradation of the clock protein. However, depending on the model considered, the period increases, decreases or passes through a maximum as a function of the protein degradation rate. We clarify the bases for these markedly different results by bringing to light the roles of (i) protein phosphorylation, which is required for protein degradation, and (ii) the velocity and degree of saturation of mRNA and protein degradation. Changes in the parameter values of the more complex of the minimal models can produce the period profiles observed in the other two models. The analysis allows us to reconcile the contradictory predictions for the dependence of the period on the clock protein degradation rate in three minimal models used to describe circadian rhythms.

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“…These negative factors, which physically interact with each other, producing heterodimers (e.g. mouse PER-CRY, or fly PER-TIM), are later shuttled back to the nucleus where they repress the positive circadian transcription factors, thereby downregulating their own transcription (Darlington et al 1998;Kume et al 1999;Lee et al 2000;Alabadi et al 2001). The decrease in abundance in the negative factors later in the circadian cycle gradually leads to their own derepression, allowing the positive transcription factor to drive a new circadian cycle.…”

Section: Circadian Clocks: Posttranscriptional and Translational Regumentioning

confidence: 99%

The role of microRNAs (miRNA) in circadian rhythmicity

Pegoraro

Tauber

2008

J Genet

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MicroRNA (miRNA) is a recently discovered new class of small RNA molecules that have a significant role in regulating gene and protein expression. These small RNAs (∼22 nt) bind to 3 untranslated regions (3 UTRs) and induce degradation or repression of translation of their mRNA targets. Hundreds of miRNAs have been identified in various organisms and have been shown to play a significant role in development and normal cell functioning. Recently, a few studies have suggested that miRNAs may be an important regulators of circadian rhythmicity, providing a new dimension (posttranscriptional) of our understanding of biological clocks. Here, we describe the mechanisms of miRNA regulation, and recent studies attempting to identify clock miRNAs and their function in the circadian system. [Pegoraro M. and Tauber E. 2008 The role of microRNAs (miRNA) in circadian rhythmicity. J. Genet. 87,[505][506][507][508][509][510][511]

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Interconnected Feedback Loops in the Neurospora Circadian System

Cited by 327 publications

References 28 publications

Tagging target genes of the MAT1-2-1 transcription factor in Fusarium verticillioides (Gibberella fujikuroi MP-A)

Tagging target genes of the MAT1-2-1 transcription factor in Fusarium verticillioides (Gibberella fujikuroi MP-A)

Dependence of the period on the rate of protein degradation in minimal models for circadian oscillations

The role of microRNAs (miRNA) in circadian rhythmicity

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