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. (paper)