Timescale of degradation-driven protein level fluctuation in the yeast Saccharomyces cerevisiae.
Abstract:
Generating robust, predictable perturbations in cellular protein levels will advance our understanding of protein function and enable control of physiological outcomes in biotechnology applications. Previous studies have shown that controlling RNA transcription achieves perturbations in protein levels over a timescale of several hours. Here, we demonstrate the potential for harnessing the protein degradation machinery to achieve robust, rapid control of a specific protein level in the yeast Saccharomyces cerevisiae. Using a light-driven protein degradation machinery and red fluorescent proteins as reporters, we show that under constant transcriptional induction, repeated triangular fluctuations in protein levels can be generated by controlling the protein degradation rate. Consistent with previous results using transcriptional control, we observed a continuous decrease in the magnitude of fluctuations as the modulation frequency increased, indicating low-pass filtering of input perturbation. However, compared to hour-scale fluctuations observed using transcriptional control, modulating the protein degradation rate enabled five to ten minute-scale fluctuations. Our study demonstrates the potential for repeated control of protein levels by controlling protein degradation rate, at timescales much shorter than that achieved by transcriptional control.
