?Modeling the effects of translational repression on the molecular circadian clock

CONDAT, C.A.; NIETO, P. S

Simposio; Simposio Latinoamericano de Cronobiologia (LASC); 2017

Organisms have evolved in a daily cyclic environment and, as consequence, developed circadian cell-autonomous clocks that temporally organize a wide range of biological processes. Transcriptional regulation is only one of many layers of circadian regulation of gene expression. Indeed, translation is also a highly regulated process that impacts on the molecular circadian clock dynamics. Translational activation of clock transcripts has been described for flies and mammals and we have previously reported the dynamical changes of the clockwork using a basic core clock theoretical model. Translational repression, on the other hand, is a much less understood process, mainly associated to the activity of microRNAs (miRNAs) at the initiation step of translation. In this work we use a theoretical model of the circadian molecular clock to study the effect of translational repression on the molecular clock dynamics. Because translational repression impacts on the translational kinetics and regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed, our approach has been to model the translational repression by introducing a threshold to the kinetics of translation. We show how the parameters associated to translation kinetics affect the period, amplitude and waveform of oscillations. We also characterize the time delays between clock mRNA and clock protein expression. Taking into account all these results we propose that a slight translational repression favor the emergence of circadian molecular oscillations.