Translational fidelity and mistranslation in the cellular response to stress

Abstract

Faithful translation of mRNA into the corresponding polypeptide is a complex multistep process, requiring accurate amino acid selection, transfer RNA (tRNA) charging and mRNA decoding on the ribosome. Key players in this process are aminoacyl-tRNA synthetases (aaRSs), which not only catalyse the attachment of cognate amino acids to their respective tRNAs, but also selectively hydrolyse incorrectly activated non-cognate amino acids and/or misaminoacylated tRNAs. This aaRS proofreading provides quality control checkpoints that exclude non-cognate amino acids during translation, and in so doing helps to prevent the formation of an aberrant proteome. However, despite the intrinsic need for high accuracy during translation, and the widespread evolutionary conservation of aaRS proofreading pathways, requirements for translation quality control vary depending on cellular physiology and changes in growth conditions, and translation errors are not always detrimental. Recent work has demonstrated that mistranslation can also be beneficial to cells, and some organisms have selected for a higher degree of mistranslation than others. The aims of this Review Article are to summarize the known mechanisms of protein translational fidelity and explore the diversity and impact of mistranslation events as a potentially beneficial response to environmental and cellular stress.

Large-scalein silicomutagenesis experiments reveal optimization of genetic code and codon usage for protein mutational robustness

“…Instead, the error rate in protein synthesis is higher with a value of about 10 −4 . This suggests that the mRNA translation process is the real bottleneck in proteome accuracy maintenance [57] and explains our finding that the standard genetic code evolved to primarily favor robustness against mutations caused by defaults in the translation machinery. Table 4: Mean ∆∆G (in kcal/mol) for µSBSs from M P oP obtained from SBSs at different codon positions (I, II, III).…”

Effect of cadmium on mRNA mistranslation in Saccharomyces cerevisiae

“…Translation errors may be an important component of individual variation, which may affect stress survival. Protein sequence variation caused by mistranslation, unlike stress-induced error-prone DNA replication, may be a potentially large and reversible source of cellular diversity under stress [33,46]. From our data, met15Δ exhibits stronger resistance to Cd stress in the case of exogenous Met supplementation (Figure 1) and the biosynthesis of Met is necessary for Cd-induced mistranslation ( Figure 4).…”

Increased Mistranslation ProtectsE. colifrom Protein Misfolding Stress due to Activation of a RpoS-dependent Heat Shock Response

“…Errors during protein synthesis can be the result of external stresses, such as aminoglycoside treatment [1], or failures in proofreading and protein quality control [2]. Each of these mechanisms result in the production of proteins with incorrect amino acids within the polypeptide.…”