tmRNA to the rescue: structural motives for the salvage of stalled ribosomes

Abstract

During translation, mRNA molecules are incidentally damaged, leaving the ribosome unable to reach or recognize the stop codon and thus stalled with mRNA and a potentially harmful polypeptide product attached to tRNA in the ribosomal P-site. In bacteria, a process called trans-translation has evolved, where a protein-RNA complex (smpB-tmRNA) mimicks the role of aminoacyl charged tRNA, replacing stalled tRNA in the ribosomal A-site. The ribosome then resumes protein synthesis guided by an mRNA-like portion of the tmRNA which ends with a stop codon, and codes for a peptide sequence susceptible to proteolysis, thus allowing the bacteria to salvage stalled ribosomes and degrade ill-defined and potentially harmful protein products. In this article, we will recollect how structural studies have yielded a model for how the pre-translocation stages of trans-translation employing structural mimicry. We will also discuss possible models for how the translocation may be carried out.