biostudies-literatureZhang HShenzhen Science and Technology Innovation CommissionNatural Science Foundation of Yunnan ProvinceNational Natural Science Foundation of China1501-1511https://www.ebi.ac.uk/biostudies/studies/S-EPMC8583063biostudies-literatureUnknown18(11)Among the 20 cytoplasmic aminoacyl-tRNA synthetases (aaRSs), alanyl-tRNA synthetase (AlaRS) has unique features. AlaRS is the only aaRS that exclusively recognizes a single G3:U70 wobble base pair in the acceptor stem of tRNA, which serves as the identity element for both the synthetic and the proofreading activities of the synthetase. The recognition is relaxed during evolution and eukaryotic AlaRS can mis-aminoacylate noncognate tRNAs with a G4:U69 base pair seemingly as a deliberate gain of function for unknown reasons. Unlike other class II aaRSs, dimerization of AlaRS is not necessarily required for aminoacylation possibly due to functional compensations from the C-terminal domain (C-Ala). In contrast to other 19 cytoplasmic aaRSs that append additional domains or motifs to acquire neRNA biologyThe uniqueness of AlaRS and its human disease connections.PMC8583063No. 2019FB089No. JCYJ20190807155011406No. 31971147Sun LZhang HYang XLfalseThe uniqueness of AlaRS and its human disease connections.Among the 20 cytoplasmic aminoacyl-tRNA synthetases (aaRSs), alanyl-tRNA synthetase (AlaRS) has unique features. AlaRS is the only aaRS that exclusively recognizes a single G3:U70 wobble base pair in the acceptor stem of tRNA, which serves as the identity element for both the synthetic and the proofreading activities of the synthetase. The recognition is relaxed during evolution and eukaryotic AlaRS can mis-aminoacylate noncognate tRNAs with a G4:U69 base pair seemingly as a deliberate gain of function for unknown reasons. Unlike other class II aaRSs, dimerization of AlaRS is not necessarily required for aminoacylation possibly due to functional compensations from the C-terminal domain (C-Ala). In contrast to other 19 cytoplasmic aaRSs that append additional domains or motifs to acquire ne2021-01-01T00:00:00Z2021 Nov2025-04-04T20:18:06.678Z2022-02-11T12:43:55.388ZS-EPMC85830633331738610.1080/15476286.2020.1861803