Biogenesis of glutaminyl-mt tRNAGln in human mitochondria.

Article Details

Citation

Copy to clipboard

Nagao A, Suzuki T, Katoh T, Sakaguchi Y, Suzuki T

Biogenesis of glutaminyl-mt tRNAGln in human mitochondria.

Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16209-14. doi: 10.1073/pnas.0907602106. Epub 2009 Sep 9.

PubMed ID

19805282 [ View in PubMed

]

Abstract

Mammalian mitochondrial (mt) tRNAs, which are required for mitochondrial protein synthesis, are all encoded in the mitochondrial genome, while mt aminoacyl-tRNA synthetases (aaRSs) are encoded in the nuclear genome. However, no mitochondrial homolog of glutaminyl-tRNA synthetase (GlnRS) has been identified in mammalian genomes, implying that Gln-tRNA(Gln) is synthesized via an indirect pathway in the mammalian mitochondria. We demonstrate here that human mt glutamyl-tRNA synthetase (mtGluRS) efficiently misaminoacylates mt tRNA(Gln) to form Glu-tRNA(Gln). In addition, we have identified a human homolog of the Glu-tRNA(Gln) amidotransferase, the hGatCAB heterotrimer. When any of the hGatCAB subunits were inactivated by siRNA-mediated knock down in human cells, the Glu-charged form of tRNA(Gln) accumulated and defects in respiration could be observed. We successfully reconstituted in vitro Gln-tRNA(Gln) formation catalyzed by the recombinant mtGluRS and hGatCAB. The misaminoacylated form of tRNA(Gln) has a weak binding affinity to the mt elongation factor Tu (mtEF-Tu), indicating that the misaminoacylated form of tRNA(Gln) is rejected from the translational apparatus to maintain the accuracy of mitochondrial protein synthesis.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
L-Glutamine	Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial	Protein	Humans	Unknown	Substrate	Details

Polypeptides

Name	UniProt ID
Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial	O75879	Details