Interactive Features of Proteins Composing Eukaryotic Circadian Clocks

Abstract

Research into the molecular mechanisms of eukaryotic circadian clocks has proceeded at an electrifying pace. In this review, we discuss advances in our understanding of the structures of central molecular players in the timing oscillators of fungi, insects, and mammals. A series of clock protein structures demonstrate that the PAS (Per/Arnt/Sim) domain has been used with great variation to formulate the transcriptional activators and repressors of the clock. We discuss how posttranslational modifications and external cues, such as light, affect the conformation and function of core clock components. Recent breakthroughs have also revealed novel interactions among clock proteins and new partners that couple the clock to metabolic and developmental pathways. Overall, a picture of clock function has emerged wherein conserved motifs and structural platforms have been elaborated into a highly dynamic collection of interacting molecules that undergo orchestrated changes in chemical structure, conformational state, and partners.

Diurnal regulation of RNA polymerase III transcription is under the control of both the feeding–fasting response and the circadian clock

“…At the core of this timing system is a cellular circadian clock, which consists of interconnected transcriptional and translational feedback loops (Cermakian and Sassone-Corsi 2000;Reppert and Weaver 2002;Kim et al 2014;Partch et al 2014). The main drivers of the clock are the transcription factors CLOCK and ARNTL (also known as BMAL1), which activate transcription of clock-controlled genes (CCGs) by binding as heterodimers to E-boxes located within their promoters (Gachon et al 2006;Ukai-Tadenuma et al 2008;Koike et al 2012;Crane and Young 2014). Among the CCGs, activated transcription of the Per and Cry gene families leads to the gradual accumulation of PER and CRY proteins; when these proteins reach a certain level, they heterodimerize and translocate into the nucleus, where they inactivate the CLOCK/ARNTL dimer and thereby repress transcription of their own genes.…”

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

“…Within the suprachiasmatic nuclei (SCN) of the hypothalamus, the "master clock" receives light input via the retina and communicates timing signals to "enslave" oscillators in peripheral organs (1,2). The molecular oscillator consists of interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (5). These additional layers of regulation are largely coordinated by systemic cues originating from circadian clock and/or feeding-coordinated rhythmic metabolism, allowing the adjustment of the molecular clockwork with the metabolic state of the cell (6).…”

An FIM-Based Long-Term In-Vial Monitoring System for Drosophila Larvae

“…For example, this system represents a well-suited setup to analyse the molecular regulation of circadian rhythmicity. Several mutants of genes regulating the adult circadian rhythmic are known [40]. For the gene timeless (tim), which is expressed from embryonic stages [40], different alleles are known to increase cycle frequency or to decrease it [41].…”

“…Several mutants of genes regulating the adult circadian rhythmic are known [40]. For the gene timeless (tim), which is expressed from embryonic stages [40], different alleles are known to increase cycle frequency or to decrease it [41]. However, to our knowledge these studies so far have not been extended to the larval stage.…”