Cellular Circadian Pacemaking and the Role of Cytosolic Rhythms

Experimental data highlight the limitations of the transcriptional/post-translational feedback loop (TTFL) model in understanding circadian clocks.

• Cytosolic rhythms in small signaling molecules are now recognized as central to the circadian pacemaker.
• The integration of oscillatory cytoplasmic elements with transcriptional feedback loops sustains circadian rhythms.
• Clock outputs may serve as inputs for subsequent cycles, blurring the lines between core mechanisms.
• The findings suggest an interdependence of nuclear and cytoplasmic processes in circadian timing.
• Some species' pacemakers may encompass the entire cell and its intercellular environment.

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