The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase.
Nucleic Acids Res
; 47(6): 3072-3085, 2019 04 08.
Article
em En
| MEDLINE
| ID: mdl-30952159
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA de Transferência
/
RNA de Transferência de Alanina
/
RNA Mitocondrial
/
Conformação de Ácido Nucleico
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article