Neisseria gonorrhoeae Escape from Cervical Epithelial Cells to Promote Bacterial Persistence

Cis-acting mRNA elements that promote programmed -1 ribosomal frameshifting (-1 PRF) redirect a fraction of translating ribosomes into a new reading frame. In viruses, these signals typically direct the translation of alternative protein products from a single mRNA. However, endogenous programmed frameshifts could also direct elongating ribosomes to premature termination codons, in which case the mRNAs could become targets for degradation by the nonsense mediated mRNA decay pathway (NMD). Computational analyses revealed the presence of 10,340 consensus -1 PRF signals in the Saccharomyces cerevisiae genome. Of the 6,353 yeast open reading frames (ORFs) included in this study, 1,275 are predicted to have at least one strong and statistically significant -1 PRF signal. In contrast to viral frameshifting, the predicted outcomes of nearly all of these genomic frameshift signals would direct ribosomes to premature termination codons, in theory making these mRNAs substrates for NMD. Nine of these predicted -1 PRF signals were tested empirically, eight of which promoted efficient levels of PRF in vivo. Furthermore, several of these were shown to act as mRNA destabilizing elements and were derepressed in a upf3∆ strain background. Importantly, these signals are found in genes whose mRNAs are known to be natural targets for NMD. These findings support the hypothesis that PRF may be used by cellular mRNAs to initiate “mRNA suicide”. We present a model that programmed frameshifting may act as a general posttranscriptional mechanism to control gene expression by regulating mRNA abundance. *Presenter. email address: [email protected]