Sequence-dependent noise filtering in small genetic motifs

Abstract

The rates of intracellular processes are, in general, in constant change in response to environmental signals and other internal processes. To deal with noise in the input signals, filtering and decision-making circuits are needed. Motivated by recent evidences from in vivo measurements that the rate limiting steps in transcription initiation are critical in determine RNA and protein numbers, we study the effects of these steps on the behavior of three genetic circuits: a toggle switch, a genetic amplitude filter and a genetic frequency filter. We model these circuits, and from stochastic simulations, we study the performance of the filters and the stability of the switch. We find that these features degrade as the transcript levels are lowered. These effects can be alleviated by adding rate limiting steps to the transcription initiation process. In addition, we show that some features of the filters, such as cutoff levels, are affected by changes in mRNA production dynamics as well. In conclusion, our study shows that the kinetics of transcription initiation of the genes composing these circuits, which are largely determined by the promoter sequence, can be varied within realistic parameter ranges of values to alter considerably their behaviors.