Mechanistic modeling of prokaryotic mRNA decay

A mechanistic model of gene expression was developed to test three prevailing and sliding prokaryotic mRNA decay theories: ribosome protection of mRNA from endonucleases, 5' binding and sliding of endonucleases on mRNA, and hybrid 5' binding/ribosome protection. The discrete event simulation incorporates the molecular events that determine both cellular mRNA and protein levels. A Monte Carlo technique was used to approximate the inherent randomness of the molecular processes involved in gene expression. Each of the decay theories was tested for the ability to predict the effects of ribosome loading and translation rate on mRNA stability as well as the observed 5' to 3' directionality of mRNA decay. The modeling results show that the hybrid decay mechanism best predicts the experimentally-observed mRNA decay behaviors. The 5' binding mechanism fails to adequately predict the sensitivity of mRNA stability to changes in translation rate and ribosome loading, while the ribosome protection mechanism does not correctly predict 5' to 3' decay directionality. In addition to discriminating between the three decay theories, the simulations provide insights into hybrid decay mechanism specific details such as RNase binding and cleavage characteristics. Finally, we discuss the application of the current mechanistic model for analysing and predicting expression from more complex genetic systems.