Journal Article

Aminoacylation and translational quality control strategy employed by leucyl-tRNA synthetase from a human pathogen with genetic code ambiguity

Xiao-Long Zhou, Zhi-Peng Fang, Zhi-Rong Ruan, Meng Wang, Ru-Juan Liu, Min Tan, Fabrizio Maria Anella and En-Duo Wang

in Nucleic Acids Research

Volume 41, issue 21, pages 9825-9838
Published in print November 2013 | ISSN: 0305-1048
Published online August 2013 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gkt741

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Aminoacyl-tRNA synthetases should ensure high accuracy in tRNA aminoacylation. However, the absence of significant structural differences between amino acids always poses a direct challenge for some aminoacyl-tRNA synthetases, such as leucyl-tRNA synthetase (LeuRS), which require editing function to remove mis-activated amino acids. In the cytoplasm of the human pathogen Candida albicans, the CUG codon is translated as both Ser and Leu by a uniquely evolved CatRNASer(CAG). Its cytoplasmic LeuRS (CaLeuRS) is a crucial component for CUG codon ambiguity and harbors only one CUG codon at position 919. Comparison of the activity of CaLeuRS-Ser919 and CaLeuRS-Leu919 revealed yeast LeuRSs have a relaxed tRNA recognition capacity. We also studied the mis-activation and editing of non-cognate amino acids by CaLeuRS. Interestingly, we found that CaLeuRS is naturally deficient in tRNA-dependent pre-transfer editing for non-cognate norvaline while displaying a weak tRNA-dependent pre-transfer editing capacity for non-cognate α-amino butyric acid. We also demonstrated that post-transfer editing of CaLeuRS is not tRNALeu species-specific. In addition, other eukaryotic but not archaeal or bacterial LeuRSs were found to recognize CatRNASer(CAG). Overall, we systematically studied the aminoacylation and editing properties of CaLeuRS and established a characteristic LeuRS model with naturally deficient tRNA-dependent pre-transfer editing, which increases LeuRS types with unique editing patterns.

Journal Article.  8869 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

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