As conserved enzymes with important functions, aminoacyl-tRNA synthetase are expressed ubiquitously in cells. These include cytoplasmic aminoacyl-tRNA synthetase, mitochondrial aminoacyl-tRNA synthetase and bifunctional aminoacyl-tRNA synthetase. Mitochondrial aminoacyl-tRNA synthetases catalyze the binding of amino acids with its corresponding tRNA in the mitochondria and participate in the translation of 13 subunits of oxidative phosphorylation enzyme complexes encoded by the mitochondrial genome. Mutations in genes encoding mitochondrial aminoacyl-tRNA synthase may cause a variety of genetic disorders. This review has summarized the clinical characteristics, molecular pathogenesis and treatment of genetic diseases caused by mutations of such genes.
Humans ; RNA, Transfer, Amino Acyl ; Genes, Mitochondrial ; Amino Acyl-tRNA Synthetases/genetics* ; Genome, Mitochondrial ; Mitochondria/genetics*

Unnatural amino acid orthogonal translation machinery can insert unnatural amino acids at desired sites of protein through stop codon by means of foreign orthogonal translation system composed of aminoacyl-tRNA synthetase and orthogonal tRNA genes. This new genetic engineering technology is not only a new tool for biochemical researches of proteins, but also an epoch-making technology for the development of new-type live viral vaccines. The mutated virus containing premature termination codon in genes necessary for replication can be propagated in transgenic cells harboring unnatural amino acid orthogonal translation machinery in media with corresponding unnatural amino acid, but it cannot replicate in conventional host cells. This replication-deficient virus is a new-type of live viral vaccine that possesses advantages of high efficacy of traditional attenuated vaccine and high safety of killed vaccine. This article reviews the application and prospect of unnatural amino acid orthogonal translation machinery in the development of novel replication-deficient virus vaccines.
Amino Acids ; genetics ; Amino Acyl-tRNA Synthetases ; Genetic Engineering ; Protein Engineering ; RNA, Transfer ; Viral Vaccines

Erythromycin is a macrolide antibiotic and inhibits bacterial protein synthesis by stimulating the dissociation of the peptidyl-tRNA molecule from the ribosomes during elongation. The use of macrolides has increased dramatically over the last few years and has led to an increase in bacterial resistance to these antibiotics. Bacterial resistance to erythromycin is generally conferred by the ribosome methylation and/or transport (efflux) protein genes. Among the identified erythromycin-resistant genes, erm(B) (erythromycin methylation) and mef(A) (macrolide efflux) are generally detectable in erythromycin-resistant streptococcal species. The distribution of these genes in oral streptococcal isolates has been reported in studies from other countries but has not been previously examined in a Korean study. We here examined by PCR the presence of erm(B) and mef(A) in oral streptococci isolated from Korean dental plaques. Among the 57 erythromycin-resistant strains tested, 64.9% harbored erm(B) whereas 40.4% were positive for mef(A). Eleven isolates had both the erm(B) and mef(A) genes. Twenty six isolates had only erm(B) and 12 isolates had only mef(A). Eight of the 57 strains examined were negative for both genes.
Anti-Bacterial Agents ; Bacterial Proteins ; Dissociative Disorders ; Erythromycin ; Incidence ; Macrolides ; Methylation ; Polymerase Chain Reaction ; Ribosomes ; RNA, Transfer, Amino Acyl

OBJECTIVETo explore the prevalence and the clinical characteristics of mitochondrial gene mutation A3243G (mt tRNA(Leu(UUR)) 3243 A-->G) in patients with type 2 diabetes mellitus (DM2) in China.

METHODSFour hundred and twenty-eight cases of DM2 patients were selected randomly. One hundred and eighty-eight individuals were healthy controls. The mutation was assayed by PCR-restriction fragment length polymorphism technique. The target fragments of PCR were digested with restriction endonuclease Apa I.

RESULTSmt tRNA(Leu(UUR)) 3243A-->G gene mutation was found in 2 of 428 patients with DM2, but not found in the controls. Further investigation of the relatives of the 2 patients' families revealed that 3 members were the carriers of mt tRNA A3243G gene mutation and the patients with diabetes. In addition, one proband and her son were characterized with the syndrome of mitochondrial encephalomyopathy with lactic acidosis. The diabetes of these patients is frequently accompanied by hearing impairment or deafness with maternal inheritance.

CONCLUSIONThe prevalence of the mitochondrial gene A3243G mutation is 0.47% in DM2 patients in China. The data acquired in this study suggest that the clinical phenotype of these patients with A3243G should be heterogeneous.

Adult ; Aged ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; RNA, Transfer, Amino Acyl ; genetics

OBJECTIVETo study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China.

METHODSThe mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members.

RESULTSThirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents.

CONCLUSIONThe mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Diabetes Mellitus ; genetics ; Genetic Testing ; Hearing Loss, Sensorineural ; genetics ; Humans ; Insulin Resistance ; genetics ; Molecular Sequence Data ; Mutation ; Prevalence ; RNA, Transfer, Amino Acyl ; genetics