Cross-editing by a tRNA synthetase allows vertebrates to abundantly express mischargeable tRNA without causing mistranslation. Issue 12 (2nd June 2020)

• Record Type: Journal Article
• Authors: Chen, Meirong; Kuhle, Bernhard; Diedrich, Jolene; Liu, Ze; Moresco, James J; Yates III, John R; Pan, Tao; Yang, Xiang-Lei
• Is Part Of: Nucleic acids research. Volume 48:Issue 12(2020)
• Page Start: 6445
• Page End: 6457
• Publication Date: 2020-06-02
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa469
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: The accuracy in pairing tRNAs with correct amino acids by aminoacyl-tRNA synthetases (aaRSs) dictates the fidelity of translation. To ensure fidelity, multiple aaRSs developed editing functions that remove a wrong amino acid from tRNA before it reaches the ribosome. However, no specific mechanism within an aaRS is known to handle the scenario where a cognate amino acid is mischarged onto a wrong tRNA, as exemplified by AlaRS mischarging alanine to G4:U69-containing tRNA Thr . Here, we report that the mischargeable G4:U69-containing tRNA Thr are strictly conserved in vertebrates and are ubiquitously and abundantly expressed in mammalian cells and tissues. Although these tRNAs are efficiently mischarged, no corresponding Thr-to-Ala mistranslation is detectable. Mistranslation is prevented by a robust proofreading activity of ThrRS towards Ala-tRNA Thr . Therefore, while wrong amino acids are corrected within an aaRS, a wrong tRNA is handled in trans by an aaRS cognate to the mischarged tRNA species. Interestingly, although Ala-tRNA Thr mischarging is not known to occur in bacteria, Escherichia coli ThrRS also possesses robust cross-editing ability. We propose that the cross-editing activity of ThrRS is evolutionarily conserved and that this intrinsic activity allows G4:U69-containing tRNA Thr to emerge and be preserved in vertebrates to have alternative functions without compromising translational fidelity.