Abstract
SummaryCircadian protein oscillations are maintained by the lifelong repetition of protein production and degradation in daily balance. It comes at the cost of ever-replayed, futile protein synthesis each day. This biosynthetic cost with a given oscillatory protein profile is relievable by a rhythmic, not constant, degradation rate that selectively peaks at the right time of day but remains low elsewhere, saving much of the gross protein loss and of the replenishing protein synthesis. Here, our mathematical modeling reveals that the rhythmic degradation rate of proteins with circadian production spontaneously emerges under steady and limited activity of proteolytic mediators and does not necessarily require rhythmic post-translational regulation of previous focus. Additional (yet steady) post-translational modifications in a proteolytic pathway can further facilitate the degradation's rhythmicity in favor of the biosynthetic cost saving. Our work is supported by animal and plant circadian data, offering a generic mechanism for potentially widespread, time-dependent protein turnover.
Highlights
Circadian clocks in various organisms generate endogenous molecular oscillations with $24-h periodicity, enabling physiological adaptation to diurnal environmental changes caused by the Earth’s rotation around its axis
It comes at the cost of ever-replayed, futile protein synthesis each day
This biosynthetic cost with a given oscillatory protein profile is relievable by a rhythmic, not constant, degradation rate that selectively peaks at the right time of day but remains low elsewhere, saving much of the gross protein loss and of the replenishing protein synthesis
Summary
Circadian clocks in various organisms generate endogenous molecular oscillations with $24-h periodicity, enabling physiological adaptation to diurnal environmental changes caused by the Earth’s rotation around its axis. We previously demonstrated that these daily rounds might be a burden to the case of highly oscillatory proteins with sharp waveforms, because establishing these waveforms requires rapid protein degradation at their falling phases (even involving the examples of sub-hour-long protein half-lives) and thereby substantial proteosynthesis for their replenishment (Figure 1C and STAR Methods, relationship between protein abundance profiles and biosynthetic costs) (Jo et al, 2018) In this context, our aforementioned notion, the price of daily biological rhythms, refers to the inevitable expense of protein synthesis in maintaining lifelong circadian rhythms of a given organism. As mathematically proven in our previous study (Jo et al, 2018), constant half-life indicates a constantly short-lived protein, which is degraded all the time at least as rapidly as required at the falling phase of the oscillation
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