Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora

Abstract

Circadian clocks are self-sustained oscillators modulating rhythmic transcription of large numbers of genes. Clock-controlled gene expression manifests in circadian rhythmicity of many physiological and behavioral functions. In eukaryotes, expression of core clock components is organized in a network of interconnected positive and negative feedback loops. This network is thought to constitute the pacemaker that generates circadian rhythmicity. The network of interconnected loops is embedded in a supra-net via a large number of interacting factors that affect expression and function of core clock components on transcriptional and post-transcriptional levels. In particular, phosphorylation and dephosphorylation of clock components are critical processes ensuring robust self-sustained circadian rhythmicity and entrainment of clocks to external cues. In cyanobacteria, three clock proteins have the capacity to generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation independent of transcription and translation. This phosphorylation rhythm regulates the function of these clock components, which then facilitate rhythmic gene transcription, including negative feedback on their own genes. In this article, we briefly present the mechanism of clock function in cyanobacteria. We then discuss in detail the contribution of transcriptional feedback and protein phosphorylation to various functional aspects of the circadian clock of Neurospora crassa.Circadian rhythms are found in numerous light-perceiving organisms including cyanobacteria, algae, fungi, plants, insects, and vertebrates. The rhythms are supported by cell-autonomous circadian clocks, which regulate expression of a large number of genes on the level of transcription (for review, see Transcriptional/translational feedback loops are hallmarks of circadian clocks in all organisms. In eukaryotes, expression of core clock components is organized in a complex network of interconnected positive and negative feedback loops (for review, see Dunlap and Loros 2004;Gachon et al. 2004;Hardin 2005). This network of gene expression is assumed to generate circadian rhythmicity. Elimination of key components of these interconnected loops disrupts many, if not all, rhythmic outputs, depending on the organism. Expression, subcellular localization, assembly, function, and turnover of clock components are crucial for circadian rhythmicity, and thus, the core clock is embedded in a supra-net of cellular machinery regulating various aspects of clock function. Protein phosphorylation and dephosphorylation are important regulatory mechanisms that are critical for self-sustained circadian rhythmicity and entrainment of clocks to external cues. It is unclear to what extent reversible phosphorylations are mechanistically instrumental for generation of rhythmicity in eukaryotic clocks.Recent findings have shown that clock proteins in cyanobacteria generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation, which is independent of tra...

Rhythmic Conidiation in Constant Light inVividMutants ofNeurospora crassa

“…There are also positive feedback mechanisms involving the influence of frq expression on wc-1 and wc-2 activity and an important role played by post-translational modifications and protein degradation. Details may be found in recent reviews (Lakin-Thomas and Brody 2004;Liu 2005;Brunner and Schafmeier 2006;Dunlap 2006;Liu and Bell-Pedersen 2006).…”

Biphasic responses in multi-site phosphorylation systems

“…Such multi-site modifications are widespread in cellular biology with multi-site modifications playing important regulatory roles in many contexts and in many cell types [1,2]. They are believed to play important roles in inflammation pathways and are implicated in important disorders [3][4][5]. The multi-site modification status of a protein has been referred to as a dynamic 'molecular barcode', controlling signal transduction and downstream effects.…”

Circadian Rhythms in Neurospora crassa: Clock Mutant Effects in the Absence of a frq-Based Oscillator

“…More details, in a recent review of the proteins involved in the Neurospora clock function, are found in an up-to-date and clear summary (Dunlap 2006). Other recent articles and reviews provide further information (Brunner and Schafmeier 2006;de Paula et al 2006;Liu and Bell-Pedersen 2006). In addition, a review of the Neurospora rhythm indicates that its inherent complexities are characteristic of a multioscillator system (Lakin-Thomasand Brody 2004).…”