Non-transcriptional processes in circadian rhythm generation

‘Biological clocks’ orchestrate mammalian biology to a daily rhythm. Whilst ‘clock gene’ transcriptional circuits impart rhythmic regulation to myriad cellular systems, our picture of the biochemical mechanisms that determine their circadian (∼24 hour) period is incomplete. Here we consider the evidence supporting different models for circadian rhythm generation in mammalian cells in light of evolutionary factors. We find it plausible that the circadian timekeeping mechanism in mammalian cells is primarily protein-based, signalling biological timing information to the nucleus by the post-translational regulation of transcription factor activity, with transcriptional feedback imparting robustness to the oscillation via hysteresis. We conclude by suggesting experiments that might distinguish this model from competing paradigms.