Modeling the translational regulation of the Drosophila clock gene Period

NIETO, P.S.; REVELLI, J.A.; GARBARINO-PICO, E.; CONDAT, C.A.; GUIDO, M. E.; TAMARIT, F.A.

Tunuyan

Simposio; XII Latin American Symposium on Chronobiology; 2013

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. At the molecular level, the circadian timekeeping is sustained by interlocking transcriptional-translational feedback loops which drive the rhythmic expression of clock components (clock mRNAs and their proteins) and other genes, to regulate cell physiology and metabolism. In recent years an increasing number of studies have highlighted the importance of translational regulation in the molecular clock. Here we present a mathematical model of the molecular circadian clock in which the synthesis of the clock protein PERIOD (PER) is achieved by a mechanism involving translational regulators (R) which enhance PER translation. We present a detailed characterization of the dynamical behavior of our model and compared its results with those obtained in previous models. We found that circadian oscillations emerge within certain ranges of R-associated parameter values; however, the period, amplitude and phase lag between per mRNA and its protein expression, vary depending on the parameters associated to PER translation. We analized the sensitivity of our model regarding control parameters like the PER degradation rate, and showed that our results agree with some recent experimental observations reported for Drosophila melanogaster.