The tmRNA System for Translational Surveillance and Ribosome Rescue

Abstract

The tmRNA system performs translational surveillance and ribosome rescue in all eubacteria and some eukaryotic organelles. This system intervenes when ribosomes read to the 3′ end of an mRNA or pause at internal codons with subsequent mRNA cleavage. A complex of alanyl-tmRNA (which functions as a tRNA and mRNA), SmpB protein, and EF-Tu•GTP binds stalled ribosomes, the nascent polypeptide is transferred to the alanine on tmRNA, and translation switches from the original message to a short tmRNA open reading frame (ORF) that encodes a degradation tag. Translation of the ORF and normal termination releases the tagged polypeptide for degradation and permits disassembly and recycling of ribosomal subunits for new rounds of protein synthesis. Structural and biochemical studies suggest mechanisms that keep tmRNA from interrupting normal translation and target ribosomes stalled with very short 3′ mRNA extensions. Additional biological roles of tmRNA include stress management and the regulation of transcriptional circuits.