Fig. 1.

The Vehicle Cargo Hypothesis. Likened to increasing traffic at the two “rush” hours at each dawn and dusk on the highway, 12-h rhythms of CEDIF gene expression peaking at dawn (ZT0) and dusk (ZT12) imply the existence of a 12-h oscillation of the trafficking capacity of the genetic information flow that also peaks at ZT0 and ZT12 in mammalian cells. The CEDIF encompasses the progressive molecular processing steps from transcription initiation, mRNA processing, ribosome biogenesis, translation, all the way to protein folding/processing/sorting in the ER and Golgi. At this point, it remains to be determined whether it is the total number of molecules that undergo processing or the metabolic rate of processing (or both) that exhibits a 12-h oscillation. The 12-h rhythms of CEDIF gene expression is in turn transcriptionally regulated by the XBP1s expression/activity, which also peaks at ZT0 and ZT12