The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase
The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase
复制标题
人线粒体丙氨酰-tRNA合成酶对G3-U70独立的tRNA识别
DOI：
10.1093/nar/gkz078
复制
发表时间：
2019
影响因子：
14.9
通讯作者：
Zhou Xiao-Long
中科院分区：
文献类型：
--
作者：
Zeng Qi-Yu;Peng Gui-Xin;Li Guang;Zhou Jing-Bo;Zheng Wen-Qiang;Xue Mei-Qin;Wang En-Duo;Zhou Xiao-Long
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.
