In chronobiology, there is a major focus on the type of molecular machinery and the rate of transcriptional and translational events that drive circadian timekeeping. Here’s a brief schematic of the respective negative and positive transcription factors that are largely involved in setting the a clock’s time near 24 hr in a mammalian circadian timing system.
The exact molecular machinery are not conversed across phyla (Drosophila vs. Homo sapien), but the operations of each phyla’s molecular machineries’ transcription and translation are comparable.
However, in this week’s edition of Nature, a group of chronobiologists from Cambridge have challenged the prevailing view that transcriptional and translational events are necessary for robust circadian timekeeping through the discovery of circadian entrainable and adaptable phenomena in HUMAN red blood cells and a unicellular alga, which are anucleate (fun fact!). Here, I report the findings from the human work as the clinical and scientific relevance of this work are HUGE!!!!
The chronobiologists specifically looked the circadian entrainment of peroxiredoxin [PRX] oxidation (say that ten times fast) and of its associated metabolites under a 12 hr high and 12 hr low thermocycle and under constant temperature conditions. As you see here, not only did PRX oxidation entrain to the thermocycle, but the circadian rhythm of PRX oxidation, which peaks at ZT 16 or 4 hrs into the lower temperature ranges, persisted under constant conditions! This entrainment was also seen for the classic NADH to NADPH oxidation-redox reaction associated with PRX oxidation.
To lend further credence to this revolutionary discovery, the chronobiologists also treated the anucleate red blood cells with an antibiotic, which can initiate transcription, to see if adding a transcriptional element would attenuate or impair this circadian entrainment……NOPE!!!!
Another series of experiments presented later in the paper illustrated that circadian timekeeping driven by non-transcriptional or transcriptional machinery is truly contingent on whether the cell is anucleate or nucleated, respectively. For example, if transcriptional-translational molecular feedback loops are disrupted (i.e. knocked-down) in a nucleated cell, then circadian timekeeping goes awry, and same for the disruption of non-transcriptional events in anucleated cells.
It’s unfortunate that us chronobiologists have to wait another year for our biennial rhythms meeting because this may take over the current discussion about extra-SCN circadian clock oscillators that are being presented and/or refuted.
O’Neill JS, & Reddy AB (2011). Circadian clocks in human red blood cells. Nature, 469 (7331), 498-503 PMID: 21270888