A Role for REP Sequences in Regulating Translation

REP sequences are highly structured elements found downstream of ∼500 genes in Escherichia coli that result in extensive stem-loop structures in their mRNAs. However, their physiological role has remained elusive. Here, we show that REP sequences can down-regulate translation, but only if they are within 15 nt of a termination codon; a spacing of 16 nt has no effect suggesting that the REP element acts to stall ribosome movement. Ribosome stalling leads to cleavage of the mRNA and induction of the trans-translation process. Using nrdAB as a model, we find that its regulation can be partially reversed by overexpression of RNA helicases, and can be fully overcome upon UV stress, emphasizing the importance of this regulatory process. Since 50% of REP-associated genes have these elements within the critical 15 nt, these findings identify a regulatory mechanism with the potential to affect translation from a large number of genes. •REP sequences down-regulate translation, but only when within 15 nt of a stop codon•REP-dependent translational regulation requires trans-translation•Overexpression of RNA helicases or UV stress reverse REP-dependent regulation•This work identifies a regulatory process that can alter translation of many genes