The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase
Autor: | Mei-Qin Xue, Jing-Bo Zhou, En-Duo Wang, Xiao-Long Zhou, Gui-Xin Peng, Wen-Qiang Zheng, Qi-Yu Zeng, Guang Li |
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Rok vydání: | 2019 |
Předmět: |
Models
Molecular RNA Mitochondrial Base pair RNA Transfer Ala Wobble base pair Mitochondrion medicine.disease_cause Substrate Specificity 03 medical and health sciences 0302 clinical medicine RNA Transfer Catalytic Domain Escherichia coli Genetics medicine Humans Base Pairing 030304 developmental biology chemistry.chemical_classification 0303 health sciences Mutation biology Nucleic Acid Enzymes Alanine-tRNA Ligase RNA Active site Kinetics Enzyme chemistry Transfer RNA biology.protein Nucleic Acid Conformation 030217 neurology & neurosurgery |
Zdroj: | Nucleic Acids Research |
ISSN: | 1362-4962 0305-1048 |
Popis: | Alanyl-tRNA synthetases (AlaRSs) from three domains of life predominantly rely on a single wobble base pair, G3-U70, of tRNAAla as a major determinant. However, this base pair is divergent in human mitochondrial tRNAAla, but instead with a translocated G5-U68. How human mitochondrial AlaRS (hmtAlaRS) recognizes tRNAAla, in particular, in the acceptor stem region, remains unknown. In the present study, we found that hmtAlaRS is a monomer and recognizes mitochondrial tRNAAla in a G3-U70-independent manner, requiring several elements in the acceptor stem. In addition, we found that hmtAlaRS misactivates noncognate Gly and catalyzes strong transfer RNA (tRNA)-independent pre-transfer editing for Gly. A completely conserved residue outside of the editing active site, Arg663, likely functions as a tRNA translocation determinant to facilitate tRNA entry into the editing domain during editing. Finally, we investigated the effects of the severe infantile-onset cardiomyopathy-associated R592W mutation of hmtAlaRS on the canonical enzymatic activities of hmtAlaRS. Overall, our results provide fundamental information about tRNA recognition and deepen our understanding of translational quality control mechanisms by hmtAlaRS. |
Databáze: | OpenAIRE |
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