Circadian Oscillators: Around the Transcription–Translation Feedback Loop and on to Output

Abstract

From cyanobacteria to mammals, organisms have evolved timing mechanisms to adapt to environmental changes in order to optimize survival and improve fitness. To anticipate these regular daily cycles, many organisms manifest near 24-h cell-autonomous oscillations that are sustained by transcription–translation-based or post-transcriptional negative feedback loops that control a wide range of biological processes. With an eye to identifying emerging common themes among cyanobacterial, fungal and animal clocks, some major recent developments in the understanding of the mechanisms that regulate these oscillators and their output are discussed. These include roles for antisense transcription, intrinsically disordered proteins, codon bias in clock genes, and a more focused discussion of post-transcriptional and translational regulation as a part of both the oscillator and output.

Macromolecular Assemblies of the Mammalian Circadian Clock

“…Such clocks are found in animals, plants, fungi, and cyanobacteria (Hurley et al, 2016). They likely represent ancient timekeeping mechanisms important for predicting daily environmental cycles on a rotating planet.…”

Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways

“…The regulatory architecture of the clock is conserved between fungi and animals; at its core is a transcription-translation negative feedback loop (TTFL) involving a heterodimeric transcription-factor complex that functions as the positive arm and a distinct protein complex, the negative arm, whose function is to inhibit the transcriptional activity of the positive arm (Figure 1A; Dunlap and Loros, 2018; Hurley et al, 2016). …”

Just-So Stories and Origin Myths: Phosphorylation and Structural Disorder in Circadian Clock Proteins

“…Just-so stories, indeed. Anyway, as I was saying, clues had been building that the dogma was incomplete (for review, see Hurley et al, 2016; Larrondo et al, 2015). The initial impetus to revising the dogma came from Neurospora , the tractable and durable model for clocks in animals and fungi, where, for instance, the molecular basis of light-resetting was first understood.…”