Cell-specific differences in the requirements for translation quality control.
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 alpha-subunits contain the active site and the beta-subunits harbor the editing site. In contrast, mitochondrial PheRS (mtPheRS) is an alpha-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 approximately 7,300 Phe-tRNA(Phe), compatible with an error rate in translation of approximately 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.
Reynolds
Noah M
NM
Department of Microbiology, Center for RNA Biology, Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA.
Ling
Jiqiang
J
Roy
Hervé
H
Banerjee
Rajat
R
Repasky
Sarah E
SE
Hamel
Patrice
P
Ibba
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D010652:Phenylalanine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D011786:Quality Control; D012343:RNA, Transfer / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D012343:RNA, Transfer; D010652:Phenylalanine-tRNA Ligase