Dynamical effects of transcriptional pause-prone sites.

We study how long pause-prone sites, commonly sequence-dependent, affect transcription and RNA temporal levels in a delayed stochastic model of transcription at the single nucleotide level. We vary pause propensity, duration and the probability of premature termination of elongation at the pause site. We also study the effects of multiple pause sites. We show that pause sites can be used to fine-tune noise strength and burst size distribution of RNA levels. Varying pause rate and duration alone affects bursting but noise is not significantly affected. Noise strength can be changed by varying both parameters and, even more pronouncedly, by varying the probability of premature termination. Adding multiple pause sites amplifies the increase in noise and bursting. This regulatory mechanism of noise and bursting, being evolvable, may partially explain how different genes exhibit a wide spectrum of different behaviors. The results might assist the engineering of genes with a desired degree of noise. Copyright 2010 Elsevier Ltd. All rights reserved.