Non-transcriptional oscillators in circadian timekeeping

Circadian clocks have evolved as an adaptation to life on a rotating planet, and orchestrate rhythmic changes in physiology to match the time of day. For decades, cellular circadian rhythms were considered to solely result from feedback between the products of rhythmically expressed genes. These transcriptional/translational feedback loops (TTFLs) have been ubiquitously studied, and explain the majority of circadian outputs. In recent years, however, non-transcriptional processes were shown to be major contributors to circadian rhythmicity. These key findings have profound implications on our understanding of the evolution and mechanistic basis of cellular circadian timekeeping. This review summarises and discusses these results and the experimental and theoretical evidence of a possible relation between non-transcriptional oscillator (NTO) mechanisms and TTFL oscillations.