A stochastic model of translation with -1 programmed ribosomal frameshifting.

Many viruses produce multiple proteins from a single mRNA sequence by encoding overlapping genes. One mechanism to decode both genes, which reside in alternate reading frames, is ?1 programmed ribosomal frameshifting. Although recognized for over 25?years, the molecular and physical mechanism of ?1 frameshifting remains poorly understood. We have developed a mathematical model that treats mRNA translation and associated ?1 frameshifting as a stochastic process in which the transition probabilities are based on the energetics of local molecular interactions. The model predicts both the location and efficiency of ?1 frameshift events in HIV-1. Moreover, we compute ?1 frameshift efficiencies upon mutations in the viral mRNA sequence and variations in relative tRNA abundances, predictions that are directly testable in experiment.