New Study Looks into the Translation Fidelity Controlled by Aminoacyl-tRNA Synthetase
Source:
Time: 2012-10-29
Aminoacylation catalyzed by aminoacyl-tRNA synthetases (aaRSs) involves covalent linkage of amino acids with their cognate tRNAs and represents the initiating step in the complex process of translation. However, the mechanism of amino acid selection and editing by eukaryotic cytoplasmic ThrRSs remains to be elucidated. Now, a new study from Chinese Academy of Sciences provides the first comprehensive elucidation of the translational fidelity control mechanism of eukaryotic Threonyl-tRNA synthetase (ThrRS).
Dr. ZHOU Xiaolong and other researchers in the lab of Prof. WANG Enduo, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, systematically analyzed the evolution of cytoplasmic ThrRSs from eukaryotes, the role of the eukaryote-specific N-extension of ThrRSs, the mis-activation of Ser, Val, Cys, Gly, Ala by S. cerevisiae ThrRS (ScThrRS); clarified the editing mechanism of ScThrRS and quantified the relative contribution of various editing pathways in total editing activity; identified the crucial nucleic acid and amino acid determinants for the editing reaction; constructed the first yeast thrS gene knockout strain and used it as a platform for the in vivo genetic assays. Importantly, they found yeast cells are tolerant of variation at the editing active sites of ScThrRS without significant Thr-to-Ser conversion in the proteome even under significant environmental stress implying checkpoints downstream of aminoacylation to provide a further quality control mechanism for the yeast translation system.
This study entitled “Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote” was published online in Nucleic Acids Research on October 23rd. It is funded by the National Natural Science Foundation of China, Ministry of Science and Technology and Chinese Academy of Sciences.
AUTHOR CONTACT:
WANG Enduo
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Schematic representation of the editing module of ScThrRS with relative contributions to total editing indicated. Pathway 1 represents kinetic proofreading after selective release into solution of Ser-AMP from the active site; pathway 2 represents tRNA-independent pre-transfer editing; pathway 3 represents tRNA-dependent pre-transfer editing; pathway 4 represents post-transfer editing. (Image provided by Prof. Enduo Wang)
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