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Two recent theoretical models, Bai et al. (2004, 2007) and Tadigotla et al. (2006), formulated thermodynamic explanations of sequence-dependent transcription pausing by RNA polymerase (RNAP). The two models differ in some basic assumptions and therefore make different yet overlapping predictions for pause locations, and different predictions on pause kinetics and mechanisms. Here we present a comprehensive comparison of the two models. We show that while they have comparable predictive power of pause locations at low NTP concentrations, the Bai et al. model is more accurate than Tadigotla et al. at higher NTP concentrations. Pausing kinetics predicted by Bai et al. is also consistent with time-course transcription reactions, while Tadigotla et al. is unsuited for this type of kinetic prediction. More importantly, the two models in general predict different pausing mechanisms even for the same pausing sites, and the Bai et al. model provides an explanation more consistent with recent single molecule observations.

Comparison of pause predictions of two sequence-dependent transcription models