Resolving Non-stop Translation Complexes - trans-Translation and Alternative Pathways

Bacteria have a particularly severe problem with non-stop translation complexes. Many ribosomes reach the end of the mRNA during translation without encountering a stop codon because bacteria do not have the mRNA proofreading mechanisms present in eukaryotes and because bacterial ribosomes do not require any information from the 3’ end of the mRNA to initiate translation. Estimates from E. coli suggest that 4% of translation initiation reactions end in non-stop complexes. At that rate, an average ribosome would have to be released from a non-stop complex 5 times per cell cycle. The trans-translation pathway appears to be the most efficient mechanism to resolve non-stop complexes. trans-Translation is mediated by tmRNA, a specialized RNA with properties of a tRNA and an mRNA, and SmpB, a small protein. Genes encoding tmRNA and SmpB have been found in every sequenced bacterial genome, indicating that trans-translation confers a selective advantage in every environment that supports bacterial life. Most of the substrates for trans-translation appear to be inadvertent non-stop complexes generated by truncated mRNAs or problems during translation. However, there are several cases in which gene expression is directed to trans-translation for regulatory reasons. In addition to trans-translation, some bacteria have alternative, protein-based pathways to resolve non-stop translation complexes. This Research Topic will explore recent discoveries and hypotheses on the mechanism and physiology of both trans-translation and alternative pathways. Questions will include how non-stop translation complexes are generated and recognized, how tmRNA-SmpB and alternative pathway components interact with ribosomes, what phenotypes result from mutations in these pathways in a wide variety of species, how these pathways can be targeted for new antibiotic development, and what can be learned from analogous systems in eukaryotes.