Abstract
ABSTRACTOscillators are essential to fuel autonomous behaviours in molecular systems. Artificial oscillators built with programmable biological molecules such as DNA and RNA are generally easy to build and tune, and can serve as timers for biological computation and regulation. We describe a new artificial nucleic acid biochemical reaction network, and we demonstrate its capacity to exhibit oscillatory solutions. This network can be built in vitro using nucleic acids and three bacteriophage enzymes, and has the potential to be implemented in cells. Numerical simulations suggest that oscillations occur in a realistic range of reaction rates and concentrations.
Highlights
All organisms require timing circuits to orchestrate processes related to their life cycle, such as cell growth, metabolism, and division [36]
Existing nucleic acid oscillators cannot be ported to the cellular environment, because they rely on the presence of multiple singlestranded or partially single-stranded DNA species, which are incompatible with the cellular machinery [15,16,19,22]
We provide below the definitions of monotone and antimonotone system
Summary
All organisms require timing circuits to orchestrate processes related to their life cycle, such as cell growth, metabolism, and division [36]. E1 produces RNA species R1 by transcribing gene g1; R1 binds to and inhibits enzyme E2, converting it to inactive enzyme E2∗ (a reaction experimentally demonstrated, for instance, in [23, 24]). Similar reactions generate inhibition and activation pathways for E1 (due to E3 and to E2, respectively) Overall, these interactions contribute to creating a negative feedback loop. RNA activators can be designed as strands whose sequences are complementary to the sequences of the inhibitors via the mechanism of strand displacement and strand titration [18,37] We previously described a two-enzyme oscillator relying on RNA aptamers [2,10]; we claim that a three-enzyme system is more tunable, and simulation results indicate that in a certain region of parameter space its amplitude can be modulated independently of the period
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