Search Our Scientific Publications & Authors

J Gene Med 2021 Apr 10;23(4):e3328. Epub 2021 Mar 10.

Department of Cardiology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Mutations in mitochondrial tRNA (mt-tRNA) genes are associated with hypertension, although their pathogenic mechanisms remain poorly understood.

Methods: In the present study, two Han Chinese families with maternally transmitted hypertension were interviewed. The mtDNA mutations of matrilineal relatives were screened by polymerase chain reaction-Sanger sequencing. Read More

NAR Genom Bioinform 2021 Mar 12;3(1):lqaa111. Epub 2021 Jan 12.

Department of Biology, Colorado State University, Fort Collins, CO, 80521 USA.

Although tRNA structure is one of the most conserved and recognizable shapes in molecular biology, aberrant tRNAs are frequently found in the mitochondrial genomes of metazoans. The extremely degenerate structures of several mitochondrial tRNAs (mt-tRNAs) have led to doubts about their expression and function. Mites from the arachnid superorder Acariformes are predicted to have some of the shortest mt-tRNAs, with a complete loss of cloverleaf-like shape. Read More

Nat Commun 2020 08 28;11(1):4269. Epub 2020 Aug 28.

Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. Read More

Elife 2020 08 19;9. Epub 2020 Aug 19.

Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.

Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3. Read More

Genet Med 2020 05 22;22(5):917-926. Epub 2020 Jan 22.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Purpose: To develop criteria to interpret mitochondrial transfer RNA (mt-tRNA) variants based on unique characteristics of mitochondrial genetics and conserved structural/functional properties of tRNA.

Methods: We developed rules on a set of established pathogenic/benign variants by examining heteroplasmy correlations with phenotype, tissue distribution, family members, and among unrelated families from published literature. We validated these deduced rules using our new cases and applied them to classify novel variants. Read More

Ir J Med Sci 2020 May 27;189(2):489-496. Epub 2019 Nov 27.

Department of Vasculocardiology, The Affiliated Hospital of Southwest Medical University, NO 25 Taiping Street, Luzhou City, 646000, Sichuan Province, China.

Objective: The objective of the study was to investigate the association between mitochondrial DNA (mtDNA) mutations and essential hypertension (EH).

Methods: One Han Chinese pedigree with maternally inherited EH was recruited in the current study. The matrilineal relatives from this family underwent clinical, genetic, and molecular analysis. Read More

Neuromuscul Disord 2019 09 21;29(9):693-697. Epub 2019 Aug 21.

Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

We report a novel mitochondrial m.4414T>C variant in the mt-tRNA (MT-TM) gene in an adult patient with chronic progressive external ophthalmoplegia and myopathy whose muscle biopsy revealed focal cytochrome c oxidase (COX)-deficient and ragged red fibres. The m. Read More

Balkan J Med Genet 2018 Jun 29;21(1):53-57. Epub 2018 Oct 29.

Department of Endocrinology and Metabolism, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, Zhengzhou People's Republic of China.

Mitochondrial DNA (mtDNA) mutations have long been proposed to play important roles in the pathogenesis of diabetes mellitus (DM). A large proportion of these mutations are localized at the genes. Owing to its high mutation rate, a growing number of mt-tRNA mutations have been reported; however some of them are neutral genetic polymorphisms and will not result in the alteration of the mitochondrial function responsible for DM. Read More

Int J Biol Sci 2018 6;14(11):1437-1444. Epub 2018 Aug 6.

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Mutations of mitochondrial transfer RNAs (mt-tRNAs) play a major role in a wide range of mitochondrial diseases because of the vital role of these molecules in mitochondrial translation. It has previously been reported that the overexpression of mitochondrial aminoacyl tRNA synthetases is effective at partially suppressing the defects resulting from mutations in their cognate mt-tRNAs in cells. Here we report a detailed analysis of the suppressive activities of mitochondrial alanyl-tRNA synthetase (AARS2) on mt-tRNA 5655 A>G mutant. Read More

BMC Genomics 2018 Jun 18;19(1):466. Epub 2018 Jun 18.

GeneCology Research Centre, Centre for Animal Health Innovation, School of Science and Engineering, University of the Sunshine Coast, Maroochydore, QLD, 4556, Australia.

Background: Mitochondrial (mt) genomes of animals typically contain 37 genes for 13 proteins, two ribosomal RNA (rRNA) genes and 22 transfer RNA (tRNA) genes. In sarcoptiform mites, the entire set of mt tRNA genes is present in Aleuroglyphus ovatus, Caloglyphus berlesei, Dermatophagoides farinae, D. pteronyssinus, Histiostoma blomquisti and Psoroptes cuniculi. Read More

J Cell Biochem 2018 07 16;119(7):6258-6265. Epub 2018 Apr 16.

School of Biological Sciences, University of the Punjab, Quaid-i-Azam Campus, Lahore, Pakistan.

Variations in mitochondrial genes have an established link with myoclonic epilepsy. In the present study we evaluated the nucleotide sequence of MT-TK gene of 52 individuals from 12 unrelated families and reported three variations in 2 of the 13 epileptic patients. The DNA sequences coding for MT-TK gene were sequenced and mutations were detected in all participants. Read More

Wellcome Open Res 2017 11;2:116. Epub 2017 Dec 11.

The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

: Gene expression in human mitochondria has various idiosyncratic features. One of these was recently revealed as the unprecedented recruitment of a mitochondrially-encoded tRNA as a structural component of the large mitoribosomal subunit. In porcine particles this is mt-tRNA whilst in humans it is mt-tRNA . Read More

Clin Exp Hypertens 2018 6;40(6):595-600. Epub 2017 Dec 6.

b Department of Ultrasound , Delta Health Hospital Shanghai , Shanghai , China.

Mutations in mitochondrial DNA, especially in mitochondrial tRNA (mt-tRNA) genes, are the important causes for maternally inherited hypertension. In this study, we reported the clinical, genetic, and molecular characterization of a Han Chinese family with hypertension. Most strikingly, this family exhibited a high penetrance and expressivity of hypertension. Read More

Am J Transl Res 2017 15;9(6):2984-2996. Epub 2017 Jun 15.

Department of Central Laboratory, Hangzhou First People's Hospital, Nanjing Medical UniversityHangzhou, China.

Polycystic ovary syndrome (PCOS) is a very common endocrine disorder affecting women of reproductive age. Insulin resistance (IR), a central component of this disease, occurs in 30%-40% of women with PCOS. To date, the molecular mechanism underlying PCOS-IR remains largely unknown. Read More

Biomolecules 2017 02 18;7(1). Epub 2017 Feb 18.

Departments of Biochemistry, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki Osaka 569-8686, Japan.

The wobble uridine (U) of transfer RNAs (tRNAs) for two-box codon recognition, i.e., tRNA, tRNA, and tRNA, harbor a sulfur- (thio-) and a methyl-derivative structure at the second and fifth positions of U, respectively. Read More

Int J Biochem Cell Biol 2017 04 9;85:106-113. Epub 2017 Feb 9.

Harry Perkins Institute of Medical Research and Centre for Medical Research, Level 7 QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands, WA 6009, Australia; School of Molecular Sciences, The University of Western Australia, Nedlands, Western Australia 6009, Australia. Electronic address:

The expression of mitochondrially-encoded genes requires the efficient processing of long precursor RNAs at the 5' and 3' ends of tRNAs, a process which, when disrupted, results in disease. Two such mutations reside within mt-tRNA; a m.3243A>G transition, which is the most common cause of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), and m. Read More

Nucleic Acids Res 2016 12 17;44(22):10974-10985. Epub 2016 Aug 17.

Division of Clinical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China

In this report, we investigated the pathogenic mechanism underlying the deafness-associated mitochondrial(mt) tRNA 7551A > G mutation. The m.7551A > G mutation is localized at a highly conserved nucleotide(A37), adjacent (3') to the anticodon, which is important for the fidelity of codon recognition and stabilization in functional tRNAs. Read More

Genet Mol Res 2016 Jun 24;15(2). Epub 2016 Jun 24.

Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Mitochondrial DNA mutations have been shown to play important roles in the pathogenesis of hepatocellular carcinoma (HCC). In particular, genes encoding mitochondrial tRNA (mt-tRNA) are hotspots for pathogenic mutations associated with HCC. Recently, an increasing number of studies have reported the involvement of such mutations in this disease. Read More

Nat Commun 2016 06 30;7:12039. Epub 2016 Jun 30.

MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.

Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Read More

PLoS One 2016 5;11(5):e0154855. Epub 2016 May 5.

Department of Pathology, Guizhou Medical University Hospital, Guizhou, Guiyang, 550004, P.R. China.

Tens of thousands of chimeric RNAs have been reported. Most of them contain a short homologous sequence (SHS) at the joining site of the two partner genes but are not associated with a fusion gene. We hypothesize that many of these chimeras may be technical artifacts derived from SHS-caused mis-priming in reverse transcription (RT) or polymerase chain reactions (PCR). Read More

Nucleic Acids Res 2016 Mar 3;44(5):2020-7. Epub 2016 Feb 3.

Department of Experimental Medical Science, Lund University, BMC B13, SE-22184 Lund, Sweden

Transfer RNAs (tRNAs) are essential for encoding the transcribed genetic information from DNA into proteins. Variations in the human tRNAs are involved in diverse clinical phenotypes. Interestingly, all pathogenic variations in tRNAs are located in mitochondrial tRNAs (mt-tRNAs). Read More

Hum Mol Genet 2016 Mar 31;25(5):903-15. Epub 2015 Dec 31.

Department of Radiology, Oncology and Pathology, Pasteur Institute-Cenci Bolognetti Foundation, Rome 00161, Italy,

Mutations in mitochondrial (mt) genes coding for mt-tRNAs are responsible for a range of syndromes, for which no effective treatment is available. We recently showed that the carboxy-terminal domain (Cterm) of human mt-leucyl tRNA synthetase rescues the pathologic phenotype associated either with the m.3243A>G mutation in mt-tRNA(Leu(UUR)) or with mutations in the mt-tRNA(Ile), both of which are aminoacylated by Class I mt-aminoacyl-tRNA synthetases (mt-aaRSs). Read More

Int J Clin Exp Med 2015 15;8(8):13341-6. Epub 2015 Aug 15.

Department of Cardiothoracic Surgery, Zhou Shan Hospital Zhou Shan, Zhejiang, China.

Alternations in mitochondrial genome resulting in mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondrial tRNA (mt-tRNA) is known for its high frequencies of polymorphisms and mutations, however, the roles of these mutations and polymorphisms in lung cancer are among heated debates. To evaluate the possible roles of reported mt-tRNA mutations in lung cancer, we examine recent published paper concerning three mt-tRNA mutations with lung cancer: A7460G in tRNA(Ser (UCN)) gene, G5563A in tRNA(Trp) gene and A12172G in tRNA(His) gene. Read More

Mitochondrial DNA A DNA Mapp Seq Anal 2016 07 10;27(4):2873-80. Epub 2015 Aug 10.

a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax , Sfax , Tunisia .

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. Read More

Front Genet 2015 23;6:113. Epub 2015 Mar 23.

Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome Rome, Italy ; Pasteur Institute-Cenci Bolognetti Foundation Rome, Italy.

Mutations in mitochondrial (mt) DNA determine important human diseases. The majority of the known pathogenic mutations are located in transfer RNA (tRNA) genes and are responsible for a wide range of currently untreatable disorders. Experimental evidence both in yeast and in human cells has shown that the detrimental effects of mt-tRNA point mutations can be attenuated by increasing the expression of the cognate mt-aminoacyl-tRNA synthetases (aaRSs). Read More

J Am Chem Soc 2015 Mar 9;137(10):3592-9. Epub 2015 Mar 9.

∥Departments of Biochemistry and Chemistry, Duke University School of Medicine, Durham, North Carolina 27710, United States.

Mammalian mitochondrial tRNA(Ser(UCN)) (mt-tRNA(Ser)) and pyrrolysine tRNA (tRNA(Pyl)) fold to near-canonical three-dimensional structures despite having noncanonical secondary structures with shortened interhelical loops that disrupt the conserved tRNA tertiary interaction network. How these noncanonical tRNAs compensate for their loss of tertiary interactions remains unclear. Furthermore, in human mt-tRNA(Ser), lengthening the variable loop by the 7472insC mutation reduces mt-tRNA(Ser) concentration in vivo through poorly understood mechanisms and is strongly associated with diseases such as deafness and epilepsy. Read More

Mitochondrial DNA A DNA Mapp Seq Anal 2016 09 28;27(5):3086-8. Epub 2015 Jan 28.

a First Affiliated Hospital of Zhengzhou University , Zhengzhou , Henan , PR China.

Recently, a growing number of reports had shown the association between mitochondrial DNA (mtDNA) sequence variants and aplastic anemia (AA). Owing to its high mutation rate, mtDNA variant had become biomarker for clinical and molecular diagnosis for AA. However, the relationship between mtDNA variant and AA was largely unknown. Read More

Mitochondrial DNA A DNA Mapp Seq Anal 2016 3;27(1):205-8. Epub 2014 Feb 3.

b Affiliated Hangzhou Hospital, Nanjing Medical University , Hangzhou , China , and.

Mitochondrial DNA mutations are increasingly recognized as an important cause of cardiovascular diseases, point mutations in mitochondrial tRNA genes being the largest group among them. Most recently, mutation at position 7501 in mt-tRNA(Ser(UCN)) gene has been reported to be associated with human cardiovascular diseases including cardiomyopathy, sudden cardiac death (SCD) and Tetralogy of Fallot (TOF). However, its direct pathogenic role remained poorly understood. Read More

EMBO Mol Med 2014 02 10;6(2):169-82. Epub 2014 Jan 10.

Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome, Italy.

Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNA(Ile) gene. Read More

EMBO Mol Med 2014 02 10;6(2):183-93. Epub 2014 Jan 10.

The Wellcome Trust Centre for Mitochondrial Research Institute for Ageing and Health The Medical School, Newcastle University, Newcastle upon Tyne, UK.

Disorders of the mitochondrial genome cause a wide spectrum of disease, these present mainly as neurological and/or muscle related pathologies. Due to the intractability of the human mitochondrial genome there are currently no effective treatments for these disorders. The majority of the pathogenic mutations lie in the genes encoding mitochondrial tRNAs. Read More