Abstract
Ribosomes that become stalled on truncated or damaged mRNAs during protein synthesis must be rescued for the cell to survive. Bacteria have evolved a diverse array of rescue pathways to remove the stalled ribosomes from the aberrant mRNA and return them to the free pool of actively translating ribosomes. In addition, some of these pathways target the damaged mRNA and the incomplete nascent polypeptide chain for degradation. This review highlights the recent developments in our mechanistic understanding of bacterial ribosomal rescue systems, including drop-off, trans-translation mediated by transfer-messenger RNA and small protein B, ribosome rescue by the alternative rescue factors ArfA and ArfB, as well as Bacillus ribosome rescue factor A, an additional rescue system found in some Gram-positive bacteria, such as Bacillus subtilis. Finally, we discuss the recent findings of ribosome-associated quality control in particular bacterial lineages mediated by RqcH and RqcP. The importance of rescue pathways for bacterial survival suggests they may represent novel targets for the development of new antimicrobial agents against multi-drug resistant pathogenic bacteria.
Highlights
When ribosomes encounter impediments during translation, they can stall on the mRNA instead of continuing protein synthesis
This study showed that alternative ribosome rescue factor A (ArfA) is essential in the absence of tmRNA, i.e., trans-translation, and vice versa
Despite the apparent similarities between ArfA and Bacillus ribosome rescue factor A (BrfA) involving regulation of expression by trans-translation, recruitment of RF2 and the KH motif, the very low sequence similarity indicates that the systems evolved independently (Shimokawa-Chiba et al, 2019)
Summary
When ribosomes encounter impediments during translation, they can stall on the mRNA instead of continuing protein synthesis. The major pathway for the rescue of non-stop ribosomal complexes is trans-translation (Figure 1C, upper panel), which was identified in >99% of bacterial genomes and is mediated by transfer-messenger RNA (tmRNA, formerly 10S, 10Sa RNA or ssrA RNA) in complex with small protein B (SmpB) (Tu et al, 1995; Keiler et al, 1996; Karzai et al, 1999; Hudson et al, 2014).
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