MT-TH

mitochondrially encoded tRNA histidine
mitochondrially encoded tRNA histidine
Identifiers
Symbol	MT-TH
Alt. symbols	MTTH
NCBI gene	4564
HGNC	7487
OMIM	590040
RefSeq	NC_001807
Other data
Locus	Chr. MT

Last updated September 07, 2022

Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene.^[1]

Structure

The MT-TH gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 69 base pairs.^[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.^[3]

Function

MT-TH is a small 69 nucleotide transfer RNA (human mitochondrial map position 12138–12206) that transfers the amino acid histidine to a growing polypeptide at the ribosomal site of protein synthesis during translation.^[4]

Clinical significance

Mutations in MT-TH can result in multiple mitochondrial deficiencies and associated disorders. MT-TH is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS),^[5]^[6] cardiomyopathy, and the MELAS/MERRF overlap syndrome.^[7]

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

A small number of people with symptoms of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have been found to have mutations in the MT-TH gene. MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.^[7]

MERRF/MELAS overlap syndrome

MELAS syndrome may also be accompanied by another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers, also known as MERRF syndrome.^[5] In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome, which is caused by mutations in the MT-TH gene. It has not been determined how such mutations alter the energy production function of the mitochondria and result in symptoms of such syndromes.^[7] A specific mutation of 12147G>A in the MT-TH gene has been found to result in the MERRF/MELAS overlap syndrome. A patient with the mutation exhibited symptoms of migrainous headache and vomiting, left hemiparesis, lateral homonymous hemianopia, and others consistent with the MERRF/MELAS overlap syndrome. The patient exhibited symptoms of MELAS first, then progressed into the overlap syndrome.^[5]

Cardiomyopathy

Mutations in the MT-TH gene may also cause cardiomyopathy, a disorder of the heart characterized by the thickening of the heart, usually in the interventricular septum, which results in a weakened heart muscle that is unable to pump blood effectively. Patients with mutations in the MT-TH gene have been found to exhibit symptoms of cardiomyopathy without other common signs of mitochondrial disease such as neurological abnormalities. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy.^[7] A specific mutation of 12192G>A in the MT-TH gene has been found in multiple patients with the disorder. patients exhibited symptoms of cardiomyopathy in different forms.^[8]

Deafness, Nonsyndromic Sensorineural, Mitochondrial

Deafness has also been associated with mutations in the MT-TH gene. Heteroplasmic 12201T>C transitions in MT-TH have been found in a family exhibiting symptoms of nonsyndromic sensorineural deafness, varying in time of onset and severity.^[9]

Related Research Articles

Leigh syndrome is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily.

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. On biopsy, the muscle tissue of patients with these diseases usually demonstrate "ragged red" muscle fibers. These ragged-red fibers contain mild accumulations of glycogen and neutral lipids, and may show an increased reactivity for succinate dehydrogenase and a decreased reactivity for cytochrome c oxidase. Inheritance was believed to be maternal. It is now known that certain nuclear DNA deletions can also cause mitochondrial myopathy such as the OPA1 gene deletion. There are several subcategories of mitochondrial myopathies.

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include MERRF syndrome, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984. A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent.

MERRF syndrome is a mitochondrial disease. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. MERRF syndrome affects different parts of the body, particularly the muscles and nervous system. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. The causes of MERRF syndrome are difficult to determine, but because it is a mitochondrial disorder, it can be caused by the mutation of nuclear DNA or mitochondrial DNA. The classification of this disease varies from patient to patient, since many individuals do not fall into one specific disease category. The primary features displayed on a person with MERRF include myoclonus, seizures, cerebellar ataxia, myopathy, and ragged red fibers (RRF) on muscle biopsy, leading to the disease's name. Secondary features include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity, or multiple lipomata. Mitochondrial disorders, including MERRFS, may present at any age.

Mitochondrially encoded 12S ribosomal RNA, also known as Mitochondrial-derived peptide MOTS-c or Mitochondrial open reading frame of the 12S rRNA-c is the SSU rRNA of the mitochondrial ribosome. In humans, 12S is encoded by the MT-RNR1 gene and is 959 nucleotides long. MT-RNR1 is one of the 37 genes contained in animal mitochondria genomes. Their 2 rRNA, 22 tRNA and 13 mRNA genes are very useful in phylogenetic studies, in particular the 12S and 16S rRNAs. The 12S rRNA is the mitochondrial homologue of the prokaryotic 16S and eukaryotic nuclear 18S ribosomal RNAs. Mutations in the MT-RNR1 gene may be associated with hearing loss.

MT-ATP6 is a mitochondrial gene with the full name 'mitochondrially encoded ATP synthase membrane subunit 6' that encodes the ATP synthase F_o subunit 6. This subunit belongs to the F_o complex of the large, transmembrane F-type ATP synthase. This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation in the electron transport chain. Specifically, one segment of ATP synthase allows positively charged ions, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP. Mutations in the MT-ATP6 gene have been found in approximately 10 to 20 percent of people with Leigh syndrome.

Mitochondrially encoded tRNA leucine 1 (UUA/G) also known as MT-TL1 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL1 gene.

MT-ND5 is a gene of the mitochondrial genome coding for the NADH-ubiquinone oxidoreductase chain 5 protein (ND5). The ND5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Variations in human MT-ND5 are associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) as well as some symptoms of Leigh's syndrome and Leber's hereditary optic neuropathy (LHON).

Mitochondrially encoded tRNA valine also known as MT-TV is a transfer RNA which in humans is encoded by the mitochondrial MT-TV gene.

Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene.

Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene. MT-TE is a small 69 nucleotide RNA that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation.

Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene.

Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene.

Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene.

Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.

Mitochondrially encoded tRNA leucine 2 (CUN) also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene.

Mitochondrially encoded tRNA asparagine also known as MT-TN is a transfer RNA which in humans is encoded by the mitochondrial MT-TN gene.

Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene.

Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene.

Mitochondrially encoded tRNA tryptophan also known as MT-TW is a transfer RNA which in humans is encoded by the mitochondrial MT-TW gene.

References

↑ Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. (April 1981). "Sequence and organization of the human mitochondrial genome". Nature. 290 (5806): 457–65. Bibcode:1981Natur.290..457A. doi:10.1038/290457a0. PMID 7219534. S2CID 4355527.
↑ "MT-TH mitochondrially encoded tRNA histidine [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
↑ "tRNA / transfer RNA | Learn Science at Scitable". www.nature.com.
↑ Blakely EL, Yarham JW, Alston CL, Craig K, Poulton J, Brierley C, et al. (September 2013). "Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease". Human Mutation. 34 (9): 1260–8. doi:10.1002/humu.22358. PMC 3884772 . PMID 23696415.
1 2 3 Melone MA, Tessa A, Petrini S, Lus G, Sampaolo S, di Fede G, et al. (February 2004). "Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype". Archives of Neurology. 61 (2): 269–72. doi: 10.1001/archneur.61.2.269 . PMID 14967777.
↑ Taylor RW, Schaefer AM, McDonnell MT, Petty RK, Thomas AM, Blakely EL, et al. (April 2004). "Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA(His) gene". Neurology. 62 (8): 1420–3. doi:10.1212/01.wnl.0000120667.77372.46. PMID 15111688. S2CID 46681236.
1 2 3 4 Reference, Genetics Home. "MT-TH gene". Genetics Home Reference.This article incorporates text from this source, which is in the public domain .
↑ Shin WS, Tanaka M, Suzuki J, Hemmi C, Toyo-oka T (December 2000). "A novel homoplasmic mutation in mtDNA with a single evolutionary origin as a risk factor for cardiomyopathy". American Journal of Human Genetics. 67 (6): 1617–20. doi:10.1086/316896. PMC 1287941 . PMID 11038324.
↑ Yan X, Wang X, Wang Z, Sun S, Chen G, He Y, et al. (October 2011). "Maternally transmitted late-onset non-syndromic deafness is associated with the novel heteroplasmic T12201C mutation in the mitochondrial tRNAHis gene". Journal of Medical Genetics. 48 (10): 682–90. doi:10.1136/jmedgenet-2011-100219. PMID 21931169. S2CID 13128611.