Function and origin of mistranslation in distinct cellular contexts

Abstract

Mistranslation describes errors during protein synthesis that prevent the amino acid sequences specified in the genetic code from being reflected within proteins. For a long time, mistranslation has largely been considered an aberrant cellular process that cells actively avoid at all times. However, recent evidence has demonstrated that cells from all three domains of life not only tolerate certain levels and forms of mistranslation, but actively induce mistranslation under certain circumstances. To this end, dedicated biological mechanisms have recently been found to reduce translational fidelity, which indicates that mistranslation is not exclusively an erroneous process and can even benefit cells in particular cellular contexts. There currently exists a spectrum of mistranslational processes that differ not only in their origins, but also in their molecular and cellular effects. These findings suggest that the optimal degree of translational fidelity largely depends on a specific cellular context. This review aims to conceptualize the basis and functional consequence of the diverse types of mistranslation that have been described so far.

Regulation of mRNA Translation in Neurons—A Matter of Life and Death

“…What translational changes occur in neurons during aging, and how distinct are these from those observed in neurodegenerative disease? Furthermore, while translational disruptions such as mistranslation and ribosomal frameshifting and pausing underlie numerous neurodegenerative conditions, growing evidence suggests that these processes also occur at low levels in healthy cells where they may serve a regulatory function (reviewed in Pan, 2013; Schwartz and Pan, 2017). Whether newly discovered translational events, such as RAN translation, are truly “non-canonical” or play a role in normal cellular function remains to be seen.…”

The influence of different types of translational inaccuracies on the genetic code structure

“…Similarly, the SGC is usually presented as a table with the unambiguous assignments but the translation process is not ideal and some errors can occur. It was estimated that one mistranslation occurs with the rate of 10 −3 to 10 −6 per codon [85] or 10 −3 to 10 −5 per amino acid [86]. Moreover, errors associated with replication and transcription processes can also change the encoded amino acid.…”

A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia

“…It ensures an optimum dynamic balance in the cellular proteome and hence overall cellular homeostasis. A multitude of factors—from aminoacyl-tRNA synthetases (aaRSs) to ribosome, as well as proteasome—play significant roles in performing this complex phenomenon 1 – 7 . A key step in this process includes decoupling of d -amino acids mischarged on tRNAs.…”

“…Consequently, errors in amino acid selection by synthetases are significantly higher (about one in 10 3 –10 2 ) than the overall error observed during translation of the genetic code (about one in 10 4 –10 3 ), thereby necessitating evolution of various cis - and trans -editing activities associated with nearly half of the known aaRSs 37 , 38 , 51 . Errors in tRNA selection, which either happen naturally and constitutively or are induced by environmental conditions (such as oxidative/temperature/antibiotic stress), have been noted in several instances, although such mistakes are not as common as those in amino acid selection 7 . However, dedicated proofreading factors for correcting mistakes in tRNA selection have not been reported till date.…”