Cell-Specific Differences in the Requirements for Translational Quality Control

Authors

Noah M. Reynolds, The Ohio State University
Jiqiang Ling, The Ohio State University
Hervé Roy, The Ohio State University
Ranat Banerjee, The Ohio State University
Sarah E. Repasky, The Ohio State University
Patrice Hamel, The Ohio State University
Michael Ibba, Chapman UniversityFollow

Document Type

Article

Publication Date

3-2-2010

Abstract

Protein synthesis has an overall error rate of approximately 10-4 for each mRNA codon translated. The fidelity of translation is mainly determined by two events: synthesis of cognate amino acid:tRNA pairs by aminoacyl-tRNA synthetases (aaRSs) and accurate selection of aminoacyl-tRNAs (aa-tRNAs) by the ribosome. To ensure faithful aa-tRNA synthesis, many aaRSs employ a proofreading (“editing”) activity, such as phenylalanyl-tRNA synthetases (PheRS) that hydrolyze mischarged Tyr-tRNA^Phe. Eukaryotes maintain two distinct PheRS enzymes, a cytoplasmic (ctPheRS) and an organellar form. CtPheRS is similar to bacterial enzymes in that it consists of a heterotetramer in which the α-subunits contain the active site and the β-subunits harbor the editing site. In contrast, mitochondrial PheRS (mtPheRS) is an α-subunit monomer that does not edit Tyr-tRNA^Phe, and a comparable transacting activity does not exist in organelles. Although mtPheRS does not edit, it is extremely specific as only one Tyr-tRNA^Phe is synthesized for every ∼7,300 Phe-tRNA^Phe, compatible with an error rate in translation of ∼10-4. When the error rate of mtPheRS was increased 17-fold, the corresponding strain could not grow on respiratory media and the mitochondrial genome was rapidly lost. In contrast, error-prone mtPheRS, editing-deficient ctPheRS, and their wild-type counterparts all supported cytoplasmic protein synthesis and cell growth. These striking differences reveal unexpectedly divergent requirements for quality control in different cell compartments and suggest that the limits of translational accuracy may be largely determined by cellular physiology.

Comments

This article was originally published in Proceedings of the National Academy of Sciences of the United States of America, volume 107, in 2010. https://doi.org/10.1073/pnas.0909640107

Recommended Citation

Reynolds, N.M., Ling, J., Roy, H., Banerjee, R., Repasky, S.E., Hamel, P. and Ibba, M. (2010) Cell-specific differences in the requirements for translational quality control. Proc. Natl. Acad. Sci. USA 107, 4063-4068. https://doi.org/10.1073/pnas.0909640107

Copyright

National Academy of Sciences