title: Aminoacylation and translational quality control strategy employed by leucyl-tRNA synthetase from a human pathogen with genetic code ambiguity.
abstract: 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 CatRNA(Ser)(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-Ser(919) and CaLeuRS-Leu(919) 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 tRNA(Leu) species-specific. In addition, other eukaryotic but not archaeal or bacterial LeuRSs were found to recognize CatRNA(Ser)(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.
authors: Center for RNA Research, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors: Xiao-Long
authors: XL
authors: Zhou
authors: Zhi-Peng
authors: ZP
authors: Fang
authors: Zhi-Rong
authors: ZR
authors: Ruan
authors: Meng
authors: M
authors: Wang
authors: Ru-Juan
authors: RJ
authors: Liu
authors: Min
authors: M
authors: Tan
authors: Fabrizio Maria
authors: FM
authors: Anella
authors: En-Duo
authors: ED
authors: Wang
mesh_terms: D000595:Amino Acid Sequence; D000613:Aminobutyrates / Q000378:metabolism; D001105:Archaea / Q000201:enzymology; D001419:Bacteria / Q000201:enzymology; D002176:Candida albicans / Q000201:enzymology; D005815:Genetic Code; D006801:Humans; D007935:Leucine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D012356:RNA, Transfer, Leu / Q000378:metabolism; D012362:RNA, Transfer, Ser / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D046249:Transfer RNA Aminoacylation; D014633:Valine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000613:Aminobutyrates; D012356:RNA, Transfer, Leu; D012362:RNA, Transfer, Ser; C012223:alpha-aminobutyric acid; C005313:norvaline; D007935:Leucine-tRNA Ligase; D014633:Valine
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